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Han Y, Kamau PM, Lai R, Luo L. Bioactive Peptides and Proteins from Centipede Venoms. Molecules 2022; 27:molecules27144423. [PMID: 35889297 PMCID: PMC9325314 DOI: 10.3390/molecules27144423] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2022] [Revised: 07/05/2022] [Accepted: 07/07/2022] [Indexed: 12/02/2022] Open
Abstract
Venoms are a complex cocktail of biologically active molecules, including peptides, proteins, polyamide, and enzymes widely produced by venomous organisms. Through long-term evolution, venomous animals have evolved highly specific and diversified peptides and proteins targeting key physiological elements, including the nervous, blood, and muscular systems. Centipedes are typical venomous arthropods that rely on their toxins primarily for predation and defense. Although centipede bites are frequently reported, the composition and effect of centipede venoms are far from known. With the development of molecular biology and structural biology, the research on centipede venoms, especially peptides and proteins, has been deepened. Therefore, we summarize partial progress on the exploration of the bioactive peptides and proteins in centipede venoms and their potential value in pharmacological research and new drug development.
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Affiliation(s)
- Yalan Han
- Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Kunming Primate Research Center, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Sino-African Joint Research Center, and Engineering Laboratory of Peptides, Kunming Institute of Zoology, Kunming 650107, China; (Y.H.); (P.M.K.)
| | - Peter Muiruri Kamau
- Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Kunming Primate Research Center, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Sino-African Joint Research Center, and Engineering Laboratory of Peptides, Kunming Institute of Zoology, Kunming 650107, China; (Y.H.); (P.M.K.)
- University of Chinese Academy of Sciences, Beijing 100049, China
| | - Ren Lai
- Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Kunming Primate Research Center, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Sino-African Joint Research Center, and Engineering Laboratory of Peptides, Kunming Institute of Zoology, Kunming 650107, China; (Y.H.); (P.M.K.)
- University of Chinese Academy of Sciences, Beijing 100049, China
- Center for Evolution and Conservation Biology, Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), Guangzhou 511458, China
- Correspondence: (R.L.); (L.L.)
| | - Lei Luo
- Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, National Resource Center for Non-Human Primates, Kunming Primate Research Center, National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Sino-African Joint Research Center, and Engineering Laboratory of Peptides, Kunming Institute of Zoology, Kunming 650107, China; (Y.H.); (P.M.K.)
- Correspondence: (R.L.); (L.L.)
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Recent Advances in Nattokinase-Enriched Fermented Soybean Foods: A Review. Foods 2022; 11:foods11131867. [PMID: 35804683 PMCID: PMC9265860 DOI: 10.3390/foods11131867] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Revised: 06/16/2022] [Accepted: 06/20/2022] [Indexed: 01/27/2023] Open
Abstract
With the dramatic increase in mortality of cardiovascular diseases (CVDs) caused by thrombus, this has sparked an interest in seeking more effective thrombolytic drugs or dietary nutriments. The dietary consumption of natto, a traditional Bacillus-fermented food (BFF), can reduce the risk of CVDs. Nattokinase (NK), a natural, safe, efficient and cost-effective thrombolytic enzyme, is the most bioactive ingredient in natto. NK has progressively been considered to have potentially beneficial cardiovascular effects. Microbial synthesis is a cost-effective method of producing NK. Bacillus spp. are the main production strains. While microbial synthesis of NK has been thoroughly explored, NK yield, activity and stability are the critical restrictions. Multiple optimization strategies are an attempt to tackle the current problems to meet commercial demands. We focus on the recent advances in NK, including fermented soybean foods, production strains, optimization strategies, extraction and purification, activity maintenance, biological functions, and safety assessment of NK. In addition, this review systematically discussed the challenges and prospects of NK in actual application. Due to the continuous exploration and rapid progress of NK, NK is expected to be a natural future alternative to CVDs.
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Seo YS, Ang MJ, Moon BC, Kim HS, Choi G, Lim HS, Kang S, Jeon M, Kim SH, Moon C, Kim JS. Protective Effects of Scolopendra Water Extract on Trimethyltin-Induced Hippocampal Neurodegeneration and Seizures in Mice. Brain Sci 2019; 9:369. [PMID: 31842431 PMCID: PMC6955677 DOI: 10.3390/brainsci9120369] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Revised: 12/05/2019] [Accepted: 12/09/2019] [Indexed: 01/15/2023] Open
Abstract
Trimethyltin (TMT) is an organotin compound with potent neurotoxic action characterized by neuronal degeneration in the hippocampus. This study evaluated the protective effects of a Scolopendra water extract (SWE) against TMT intoxication in hippocampal neurons, using both in vitro and in vivo model systems. Specifically, we examined the actions of SWE on TMT- (5 mM) induced cytotoxicity in primary cultures of mouse hippocampal neurons (7 days in vitro) and the effects of SWE on hippocampal degeneration in adult TMT- (2.6 mg/kg, intraperitoneal) treated C57BL/6 mice. We found that SWE pretreatment (0-100 μg/mL) significantly reduced TMT-induced cytotoxicity in cultured hippocampal neurons in a dose-dependent manner, as determined by lactate dehydrogenase and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide assays. Additionally, this study showed that perioral administration of SWE (5 mg/kg), from -6 to 0 days before TMT injection, significantly attenuated hippocampal cell degeneration and seizures in adult mice. Furthermore, quantitative analysis of Iba-1 (Allograft inflammatory factor 1)- and GFAP (Glial fibrillary acidic protein)-immunostained cells revealed a significant reduction in the levels of Iba-1- and GFAP-positive cell bodies in the dentate gyrus (DG) of mice treated with SWE prior to TMT injection. These data indicated that SWE pretreatment significantly protected the hippocampus against the massive activation of microglia and astrocytes elicited by TMT. In addition, our data showed that the SWE-induced reduction of immune cell activation was linked to a significant reduction in cell death and a significant improvement in TMT-induced seizure behavior. Thus, we conclude that SWE ameliorated the detrimental effects of TMT toxicity on hippocampal neurons, both in vivo and in vitro. Altogether, our findings hint at a promising pharmacotherapeutic use of SWE in hippocampal degeneration and dysfunction.
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Affiliation(s)
- Yun-Soo Seo
- Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, 111, Geonjae-ro, Naju-si 58245, Jeollanam-do, Korea; (Y.-S.S.); (B.C.M.); (H.S.K.); (G.C.); (H.-S.L.)
| | - Mary Jasmin Ang
- College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Korea; (M.J.A.); (S.K.); (M.J.); (S.-H.K.)
| | - Byeong Cheol Moon
- Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, 111, Geonjae-ro, Naju-si 58245, Jeollanam-do, Korea; (Y.-S.S.); (B.C.M.); (H.S.K.); (G.C.); (H.-S.L.)
| | - Hyo Seon Kim
- Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, 111, Geonjae-ro, Naju-si 58245, Jeollanam-do, Korea; (Y.-S.S.); (B.C.M.); (H.S.K.); (G.C.); (H.-S.L.)
| | - Goya Choi
- Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, 111, Geonjae-ro, Naju-si 58245, Jeollanam-do, Korea; (Y.-S.S.); (B.C.M.); (H.S.K.); (G.C.); (H.-S.L.)
| | - Hye-Sun Lim
- Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, 111, Geonjae-ro, Naju-si 58245, Jeollanam-do, Korea; (Y.-S.S.); (B.C.M.); (H.S.K.); (G.C.); (H.-S.L.)
| | - Sohi Kang
- College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Korea; (M.J.A.); (S.K.); (M.J.); (S.-H.K.)
| | - Mijin Jeon
- College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Korea; (M.J.A.); (S.K.); (M.J.); (S.-H.K.)
| | - Sung-Ho Kim
- College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Korea; (M.J.A.); (S.K.); (M.J.); (S.-H.K.)
| | - Changjong Moon
- College of Veterinary Medicine and BK21 Plus Project Team, Chonnam National University, Gwangju 61186, Korea; (M.J.A.); (S.K.); (M.J.); (S.-H.K.)
| | - Joong Sun Kim
- Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, 111, Geonjae-ro, Naju-si 58245, Jeollanam-do, Korea; (Y.-S.S.); (B.C.M.); (H.S.K.); (G.C.); (H.-S.L.)
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Khursade PS, Galande SH, Shiva Krishna P, Prakasham R. Stenotrophomonas maltophilia Gd2: A potential and novel isolate for fibrinolytic enzyme production. Saudi J Biol Sci 2019; 26:1567-1575. [PMID: 31762628 PMCID: PMC6864133 DOI: 10.1016/j.sjbs.2018.10.014] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Revised: 10/16/2018] [Accepted: 10/29/2018] [Indexed: 12/04/2022] Open
Abstract
The bacterium with an ability to produce extracellular fibrinolytic protease was isolated and identified as Stenotrophomonas maltophilia Gd2 based on ribotyping. The in-vitro fibrinolytic profile of this enzyme depicted 73% of fibrin clot dissolution within 4 h. Fibrinolytic enzyme yield influenced by different physiological (incubation time, temperature, agitation and pH), nutritional (macronutrients such as carbon and nitrogen sources) and biological (inoculums age and inoculums concentration) parameters of fermentation which were optimized based on one-factor-at-a-time (OFAT) approach. The enzyme yield improved from 886 to 1795 FU ml-1 upon OFAT; optimized conditions include temperature - 33 °C, pH - 8.0, incubation time - 36 h, agitation - 150 RPM, 3% v/v inoculums and age of inoculum - 18 h. Further optimization of enzyme production was achieved with implementation of Plackett-Burman media designing where the production levels increased to 3411 FU ml-1 and noticed that peptone, pH, dextrose and K2HPO4 was found to be significant factor. This ms reports the highest fibrinolytic enzyme yield with S. maltophilia to that of literature reports.
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Affiliation(s)
- Parag S. Khursade
- Organic Synthesis & Process Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India
- Academy of Scientific and Innovative Research (AcSIR), CSIR-IICT Campus, Hyderabad 500007, India
| | - Sneha H. Galande
- Organic Synthesis & Process Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India
- Academy of Scientific and Innovative Research (AcSIR), CSIR-IICT Campus, Hyderabad 500007, India
| | - P. Shiva Krishna
- Department of Micro Biology, Kakatiya University, Warangal 506009, India
| | - R.S. Prakasham
- Organic Synthesis & Process Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India
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Scolopendra subspinipes mutilans Extract Suppresses Inflammatory and Neuropathic Pain In Vitro and In Vivo. EVIDENCE-BASED COMPLEMENTARY AND ALTERNATIVE MEDICINE 2018; 2018:5057372. [PMID: 30647762 PMCID: PMC6311788 DOI: 10.1155/2018/5057372] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/04/2018] [Revised: 11/16/2018] [Accepted: 11/29/2018] [Indexed: 12/30/2022]
Abstract
Background Sciatic nerve injury develops from a variety of pathological causes, including traumatic injury and neuroinflammatory disorders, which are accompanied by pathological changes that have a critical impact on neuropathic pain and locomotor activity. Extracts of Scolopendra subspinipes mutilans (SSM) are used in traditional medicine for the treatment of a wide range of neuropathic diseases, including lower back pain, peripheral neuropathy, and sciatic nerve injury. Although SSM shows anti-inflammatory, antibacterial, and anticonvulsant activities, its diverse mechanisms of action remain unclear. Thus, the present study examined the effects of SSM in vitro and in vivo. Methods To estimate the anti-inflammatory effects of SSM, inflammatory conditions were induced using lipopolysaccharide (LPS) in RAW 264.7 cells, and inflammatory-related factors were evaluated by enzyme-linked immunosorbent assay (ELISA) and western blotting analyses. Sciatic nerve crush injury (SNCI) was induced in rats using a surgical clip instrument. The effects of SSM in the SNCI model were evaluated in behavioral tests by calculating the sciatic functional index (SFI) and measuring thermal hyperalgesia sensitivity and by monitoring inflammatory factors expression in western blotting analyses. Results We observed the anti-inflammatory effects of SSM treatment both in vitro and in vivo. The PGE2 and NO production were suppressed by SSM. Protein analyses indicated that expression of NF-κB and degradation of IκBα were suppressed by SSM treatment. In addition, the levels of iNOS, TNF-α, IL-6, and COX-2 expression were reduced by SSM treatment in RAW 264.7 cells and in the SNCI-induced animals. In behavioral studies, SSM treatment enhanced the SFI and improved the thermal sensitivity test results. Conclusions Our results suggest that SSM suppresses the production of inflammatory factors via the NF-κB pathway and accelerates the morphological and functional recovery of the peripheral nervous system. Hence, SSM may be a useful therapeutic candidate for treatment of neuropathic pain diseases.
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Arthropod venoms: Biochemistry, ecology and evolution. Toxicon 2018; 158:84-103. [PMID: 30529476 DOI: 10.1016/j.toxicon.2018.11.433] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2018] [Revised: 11/20/2018] [Accepted: 11/26/2018] [Indexed: 12/17/2022]
Abstract
Comprising of over a million described species of highly diverse invertebrates, Arthropoda is amongst the most successful animal lineages to have colonized aerial, terrestrial, and aquatic domains. Venom, one of the many fascinating traits to have evolved in various members of this phylum, has underpinned their adaptation to diverse habitats. Over millions of years of evolution, arthropods have evolved ingenious ways of delivering venom in their targets for self-defence and predation. The morphological diversity of venom delivery apparatus in arthropods is astounding, and includes extensively modified pedipalps, tail (telson), mouth parts (hypostome), fangs, appendages (maxillulae), proboscis, ovipositor (stinger), and hair (urticating bristles). Recent investigations have also unravelled an astonishing venom biocomplexity with molecular scaffolds being recruited from a multitude of protein families. Venoms are a remarkable bioresource for discovering lead compounds in targeted therapeutics. Several components with prospective applications in the development of advanced lifesaving drugs and environment friendly bio-insecticides have been discovered from arthropod venoms. Despite these fascinating features, the composition, bioactivity, and molecular evolution of venom in several arthropod lineages remains largely understudied. This review highlights the prevalence of venom, its mode of toxic action, and the evolutionary dynamics of venom in Arthropoda, the most speciose phylum in the animal kingdom.
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Devaraj Y, Rajender SK, Halami PM. Purification and characterization of fibrinolytic protease from Bacillus amyloliquefaciens MCC2606 and analysis of fibrin degradation product by MS/MS. Prep Biochem Biotechnol 2018; 48:172-180. [DOI: 10.1080/10826068.2017.1421964] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022]
Affiliation(s)
- Yogesh Devaraj
- Microbiology and Fermentation Technology Department, CSIR-Central Food Technological Research Institute, Mysore, India
| | - Savita Kumari Rajender
- Microbiology and Fermentation Technology Department, CSIR-Central Food Technological Research Institute, Mysore, India
| | - Prakash Motiram Halami
- Microbiology and Fermentation Technology Department, CSIR-Central Food Technological Research Institute, Mysore, India
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Zhao F, Lan X, Li T, Xiang Y, Zhao F, Zhang Y, Lee WH. Proteotranscriptomic Analysis and Discovery of the Profile and Diversity of Toxin-like Proteins in Centipede. Mol Cell Proteomics 2018; 17:709-720. [PMID: 29339413 DOI: 10.1074/mcp.ra117.000431] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2017] [Revised: 12/15/2017] [Indexed: 12/17/2022] Open
Abstract
Centipedes are one of the oldest venomous animals and use their venoms as weapons to attack prey or protect themselves. Their venoms contain various components with different biomedical and pharmacological properties. However, little attention has been paid to the profiles and diversity of their toxin-like proteins/peptides. In this study, we used a proteotranscriptomic approach to uncover the diversity of centipede toxin-like proteins in Scolopendra subspinipes mutilans Nine hundred twenty-three and 6,736 peptides, which were separately isolated from venom and torso tissues, respectively, were identified by ESI-MS/MS and deduced from their transcriptomes. Finally, 1369 unique proteins were identified in the proteome, including 100 proteins that exhibited overlapping expression in venom and torso tissues. Of these proteins, at least 40 proteins were identified as venom toxin-like proteins. Meanwhile, transcriptome mining identified ∼10-fold more toxin-like proteins and enabled the characterization of the precursor architecture of mature toxin-like peptides. Importantly, combined with proteomic and transcriptomic analyses, 25 toxin-like proteins/peptides (neurotoxins accounted for 50%) were expressed outside the venom gland and involved in gene recruitment processes. These findings highlight the extensive diversity of centipede toxin-like proteins and provide a new foundation for the medical-pharmaceutical use of centipede toxin-like proteins. Moreover, we are the first group to report the gene recruitment activity of venom toxin-like proteins in centipede, similar to snakes.
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Affiliation(s)
- Feng Zhao
- From the ‡Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, 32 East Jiao-Chang Road, Kunming, Yunnan 650223, China; .,§Key Laboratory of Subtropical Medicinal Edible Resources Development and Utilization in Yunnan Province, Department of Biology and Chemistry, Puer University, 6 Xueyuan Road, Puer, Yunnan 665000, China.,¶Institute of Comparative Study of Traditional Materia Medica, Institute of Integrative Medicine of Fudan University, Shanghai China
| | - Xinqiang Lan
- From the ‡Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, 32 East Jiao-Chang Road, Kunming, Yunnan 650223, China.,‖Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China
| | - Tao Li
- §Key Laboratory of Subtropical Medicinal Edible Resources Development and Utilization in Yunnan Province, Department of Biology and Chemistry, Puer University, 6 Xueyuan Road, Puer, Yunnan 665000, China.,¶Institute of Comparative Study of Traditional Materia Medica, Institute of Integrative Medicine of Fudan University, Shanghai China
| | - Yang Xiang
- From the ‡Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, 32 East Jiao-Chang Road, Kunming, Yunnan 650223, China
| | - Fang Zhao
- §Key Laboratory of Subtropical Medicinal Edible Resources Development and Utilization in Yunnan Province, Department of Biology and Chemistry, Puer University, 6 Xueyuan Road, Puer, Yunnan 665000, China.,¶Institute of Comparative Study of Traditional Materia Medica, Institute of Integrative Medicine of Fudan University, Shanghai China
| | - Yun Zhang
- From the ‡Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, 32 East Jiao-Chang Road, Kunming, Yunnan 650223, China; .,**Center for Excellence in Animal Evolution and Genetics, Chinese Academy of Sciences, Kunming 650223, China
| | - Wen-Hui Lee
- From the ‡Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences/Key Laboratory of Bioactive Peptides of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, 32 East Jiao-Chang Road, Kunming, Yunnan 650223, China;
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Purification, biochemical, and structural characterization of a novel fibrinolytic enzyme from Mucor subtilissimus UCP 1262. Bioprocess Biosyst Eng 2017; 40:1209-1219. [DOI: 10.1007/s00449-017-1781-3] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Accepted: 05/08/2017] [Indexed: 12/27/2022]
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Affiliation(s)
- Francesca L. Ware
- School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, Leicester LE12 5RD, UK
| | - Martin R. Luck
- School of Biosciences, University of Nottingham, Sutton Bonington Campus, Loughborough, Leicester LE12 5RD, UK
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Involvement of mast cells and histamine in edema induced in mice by Scolopendra viridicornis centipede venom. Toxicon 2016; 121:51-60. [DOI: 10.1016/j.toxicon.2016.08.017] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2016] [Revised: 08/17/2016] [Accepted: 08/23/2016] [Indexed: 11/17/2022]
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Abstract
INTRODUCTION Centipedes are one of the oldest and most successful lineages of venomous terrestrial predators. Despite their use for centuries in traditional medicine, centipede venoms remain poorly studied. However, recent work indicates that centipede venoms are highly complex chemical arsenals that are rich in disulfide-constrained peptides that have novel pharmacology and three-dimensional structure. Areas covered: This review summarizes what is currently known about centipede venom proteins, with a focus on disulfide-rich peptides that have novel or unexpected pharmacology that might be useful from a therapeutic perspective. The authors also highlight the remarkable diversity of constrained three-dimensional peptide scaffolds present in these venoms that might be useful for bioengineering of drug leads. Expert opinion: Like most arthropod predators, centipede venoms are rich in peptides that target neuronal ion channels and receptors, but it is also becoming increasingly apparent that many of these peptides have novel or unexpected pharmacological properties with potential applications in drug discovery and development.
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Affiliation(s)
- Eivind A B Undheim
- a Institute for Molecular Bioscience , The University of Queensland , St Lucia , Australia.,b Centre for Advanced Imaging , The University of Queensland , St Lucia , Australia
| | - Ronald A Jenner
- c Department of Life Sciences , Natural History Museum , London , UK
| | - Glenn F King
- a Institute for Molecular Bioscience , The University of Queensland , St Lucia , Australia
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Chaparro E, da Silva P. Lacrain: the first antimicrobial peptide from the body extract of the Brazilian centipede Scolopendra viridicornis. Int J Antimicrob Agents 2016; 48:277-85. [DOI: 10.1016/j.ijantimicag.2016.05.015] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2015] [Revised: 04/20/2016] [Accepted: 05/21/2016] [Indexed: 01/28/2023]
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Hakim MA, Yang S, Lai R. Centipede venoms and their components: resources for potential therapeutic applications. Toxins (Basel) 2015; 7:4832-51. [PMID: 26593947 PMCID: PMC4663536 DOI: 10.3390/toxins7114832] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2015] [Revised: 11/10/2015] [Accepted: 11/11/2015] [Indexed: 12/23/2022] Open
Abstract
Venomous animals have evolved with sophisticated bio-chemical strategies to arrest prey and defend themselves from natural predators. In recent years, peptide toxins from venomous animals have drawn considerable attention from researchers due to their surprising chemical, biochemical, and pharmacological diversity. Similar to other venomous animals, centipedes are one of the crucial venomous arthropods that have been used in traditional medicine for hundreds of years in China. Despite signifying pharmacological importance, very little is known about the active components of centipede venoms. More than 500 peptide sequences have been reported in centipede venomous glands by transcriptome analysis, but only a small number of peptide toxins from centipede has been functionally described. Like other venomous animals such as snakes, scorpions, and spiders, the venom of centipedes could be an excellent source of peptides for developing drugs for treatments as well as bio-insecticides for agrochemical applications. Although centipede venoms are yet to be adequately studied, the venom of centipedes as well as their components described to date, should be compiled to help further research. Therefore, based on previous reports, this review focusses on findings and possible therapeutic applications of centipede venoms as well as their components.
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Affiliation(s)
- Md Abdul Hakim
- Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of sciences, Kunming 650223, Yunnan, China.
- University of Chinese Academy of Sciences, Beijing100009, China.
| | - Shilong Yang
- Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of sciences, Kunming 650223, Yunnan, China.
- University of Chinese Academy of Sciences, Beijing100009, China.
| | - Ren Lai
- Key Laboratory of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, Chinese Academy of sciences, Kunming 650223, Yunnan, China.
- Joint Laboratory of Natural Peptide, University of Science and Technology of China and Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650223, China.
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Shen X, Li WQ. High-mobility group box 1 protein and its role in severe acute pancreatitis. World J Gastroenterol 2015; 21:1424-1435. [PMID: 25663762 PMCID: PMC4316085 DOI: 10.3748/wjg.v21.i5.1424] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2014] [Revised: 10/07/2014] [Accepted: 11/11/2014] [Indexed: 02/06/2023] Open
Abstract
The high mobility group box 1 (HMGB1), which belongs to the subfamily of HMG-1/-2, is a highly conserved single peptide chain consisting of 215 amino acid residues with a molecular weight of approximately 24894 Da. HMGB1 is a ubiquitous nuclear protein in mammals and plays a vital role in inflammatory diseases. Acute pancreatitis is one of the most common causes of acute abdominal pain with a poor prognosis. Acute pancreatitis is an acute inflammatory process of the pancreas (duration of less than six months), for which the severe form is called severe acute pancreatitis (SAP). More and more studies have shown that HMGB1 has a bidirectional effect in the pathogenesis of SAP. Extracellular HMGB1 can aggravate the pancreatic inflammatory process, whereas intracellular HMGB1 has a protective effect against pancreatitis. The mechanism of HMGB1 is multiple, mainly through the nuclear factor-κB pathway. Receptors for advanced glycation end-products and toll-like receptors (TLR), especially TLR-2 and TLR-4, are two major types of receptors mediating the inflammatory process triggered by HMGB1 and may be also the main mediators in the pathogenesis of SAP. HMGB1 inhibitors, such as ethyl pyruvate, pyrrolidine dithiocarbamate and Scolopendra subspinipes mutilans, can decrease the level of extracellular HMGB1 and are the promising targets in the treatment of SAP.
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Inhibitory Effects of Scolopendra Pharmacopuncture on the Development and Maintenance of Neuropathic Pain in Rats: Possible Involvement of Spinal Glial Cells. J Acupunct Meridian Stud 2015; 8:236-44. [PMID: 26433800 DOI: 10.1016/j.jams.2015.01.001] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2014] [Revised: 01/02/2015] [Accepted: 01/05/2015] [Indexed: 01/14/2023] Open
Abstract
Scolopendra extracts were used for pharmacopuncture at the Kidney 1 acupoint to investigate the role of Scolopendra pharmacopuncture (SPP) in both the development and maintenance of neuropathic pain induced by L5 spinal nerve ligation in rats and the contribution of spinal glial cells. A single treatment and five once-daily treatments with SPP were given to evaluate its effects on the development and maintenance stages of neuropathic pain, respectively, which was followed by behavioral tests. Immunohistochemistry and Western blotting tests were also carried out. A single treatment of SPP delayed spinal nerve ligation-induced mechanical allodynia and thermal hyperalgesia and induced a profound decrease in the expression of ionized calcium binding adaptor protein in the lumbar spinal cord. Repeated SPP treatments reliably suppressed mechanical allodynia and thermal hyperalgesia at later time points, and these results correlated mainly with decreases in glial fibrillary acidic protein. Intriguingly, ionized calcium binding adaptor protein expression was also reduced after repeated SPP. These results illustrate that neuropathic pain in the development and maintenance stages is alleviated by SPP treatment, which may be ascribed principally to deactivations of microglia and astroglia, respectively. Additionally, microglial inactivation seems to be partially involved in preventing neuropathic pain in the maintenance stage.
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Lee H, Hwang JS, Lee J, Kim JI, Lee DG. Scolopendin 2, a cationic antimicrobial peptide from centipede, and its membrane-active mechanism. BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES 2014; 1848:634-42. [PMID: 25462167 DOI: 10.1016/j.bbamem.2014.11.016] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/10/2014] [Revised: 11/04/2014] [Accepted: 11/17/2014] [Indexed: 11/29/2022]
Abstract
Scolopendin 2 is a 16-mer peptide (AGLQFPVGRIGRLLRK) derived from the centipede Scolopendra subspinipes mutilans. We observed that this peptide exhibited antimicrobial activity in a salt-dependent manner against various fungal and bacterial pathogens and showed no hemolytic effect in the range of 1.6 μM to 100 μM. Circular dichroism analysis showed that the peptide has an α-helical properties. Furthermore, we determined the mechanism(s) of action using flow cytometry and by investigating the release of intracellular potassium. The results showed that the peptide permeabilized the membranes of Escherichia coli O157 and Candida albicans, resulting in loss of intracellular potassium ions. Additionally, bis-(1,3-dibutylbarbituric acid) trimethine oxonol and 3,3'-dipropylthiacarbocyanine iodide assays showed that the peptide caused membrane depolarization. Using giant unilamellar vesicles encapsulating calcein and large unilamellar vesicles containing fluorescein isothiocyanate-dextran, which were similar in composition to typical E. coli O157 and C. albicans membranes, we demonstrated that scolopendin 2 disrupts membranes, resulting in a pore size between 4.8 nm and 5.0 nm. Thus, we have demonstrated that a cationic antimicrobial peptide, scolopendin 2, exerts its broad-spectrum antimicrobial effects by forming pores in the cell membrane.
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Affiliation(s)
- Heejeong Lee
- School of Life Sciences, BK 21 Plus KNU Creative BioResearch Group, College of Natural Sciences, Kyungpook National University, Daehak-ro 80, Buk-gu, Daegu 702-701, Republic of Korea
| | - Jae-Sam Hwang
- Department of Agricultural Biology, National Academy of Agricultural Science, RDA, Jeonju, Republic of Korea
| | - Jaeho Lee
- School of Life Sciences, Gwangju Institute of Science and Technology, Oryong-dong, Buk-gu, Gwangju 500-712, Republic of Korea
| | - Jae Il Kim
- School of Life Sciences, Gwangju Institute of Science and Technology, Oryong-dong, Buk-gu, Gwangju 500-712, Republic of Korea
| | - Dong Gun Lee
- School of Life Sciences, BK 21 Plus KNU Creative BioResearch Group, College of Natural Sciences, Kyungpook National University, Daehak-ro 80, Buk-gu, Daegu 702-701, Republic of Korea.
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González-Morales L, Pedraza-Escalona M, Diego-Garcia E, Restano-Cassulini R, Batista CVF, Gutiérrez MDC, Possani LD. Proteomic characterization of the venom and transcriptomic analysis of the venomous gland from the Mexican centipede Scolopendra viridis. J Proteomics 2014; 111:224-37. [PMID: 24780725 DOI: 10.1016/j.jprot.2014.04.033] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2014] [Revised: 04/16/2014] [Accepted: 04/18/2014] [Indexed: 11/29/2022]
Abstract
UNLABELLED This communication reports the results of proteomic, transcriptomic, biochemical and electrophysiological analysis of the soluble venom and venom glands of the Mexican centipede Scolopendra viridis Say (here thereafter abbreviated S. viridis). Separation of the soluble venom permitted to obtain 54 different fractions, from which a mass finger printing analysis permitted the identification of at least 86 components, where 70% of the molecules have low molecular masses. Two-dimensional electrophoretic separation of this venom revealed the presence of about forty proteins with molecular weights ranging from 17 to 58kDa. The novo sequencing of 149 peptides obtained by LC-MS/MS from the 2D-gels showed the presence of proteins with amino acid sequences similar to several enzymes and venom allergens type 3. Furthermore, a total of 180 sequences were obtained from a cDNA library prepared with two venomous glands. From this, 155 sequences correspond to complete genes containing more than 200 base pairs each. Comparative sequence analyses of these sequences indicated the presence of different types of enzymes and toxin-like genes. Two proteins with molecular weights around 37,000 and 42,000Da were shown to contain hyaluronidase activity. Electrophysiological assays performed with soluble venom show that it decreases mammalian sodium channel currents. BIOLOGICAL SIGNIFICANCE Animal venoms of Scolopendra species have been scarcely studied, although they have been reported to contain several bioactive compounds, some of which with potential therapeutic interest. The Mexican centipede S. viridis contains a powerful venom, capable of inflicting immediate effects on their preys. This communication is focused on the identification and description of a proteomic and transcriptomic analysis of the protein components of this venom. Several amino acid sequences similar to reported enzymes are the principal components in the S. viridis venom, but also a low number of toxins were identified. This knowledge should contribute to the understanding of the pharmacological effects caused by bites of this centipede species.
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Affiliation(s)
- Lidia González-Morales
- Instituto de Biotecnología, Universidad Nacional Autónoma de México, Avenida Universidad, 2001, Cuernavaca 62210, Mexico; Centro de Investigación en Biotecnología, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Mexico
| | - Martha Pedraza-Escalona
- Instituto de Biotecnología, Universidad Nacional Autónoma de México, Avenida Universidad, 2001, Cuernavaca 62210, Mexico
| | - Elia Diego-Garcia
- Instituto de Biotecnología, Universidad Nacional Autónoma de México, Avenida Universidad, 2001, Cuernavaca 62210, Mexico
| | - Rita Restano-Cassulini
- Instituto de Biotecnología, Universidad Nacional Autónoma de México, Avenida Universidad, 2001, Cuernavaca 62210, Mexico
| | - Cesar V F Batista
- Instituto de Biotecnología, Universidad Nacional Autónoma de México, Avenida Universidad, 2001, Cuernavaca 62210, Mexico
| | - Maria del Carmen Gutiérrez
- Centro de Investigación en Biotecnología, Universidad Autónoma del Estado de Morelos, Cuernavaca 62209, Mexico
| | - Lourival D Possani
- Instituto de Biotecnología, Universidad Nacional Autónoma de México, Avenida Universidad, 2001, Cuernavaca 62210, Mexico.
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Cai M, Choi SM, Song BK, Son I, Kim S, Yang EJ. Scolopendra subspinipes mutilans attenuates neuroinflammation in symptomatic hSOD1(G93A) mice. J Neuroinflammation 2013; 10:131. [PMID: 24168240 PMCID: PMC4231348 DOI: 10.1186/1742-2094-10-131] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2013] [Accepted: 10/07/2013] [Indexed: 11/23/2022] Open
Abstract
Background Amyotrophic lateral sclerosis (ALS) is a progressive, adult-onset neurodegenerative disorder characterized by selective motor neuron death in the spinal cord, brainstem, and motor cortex. Neuroinflammation is one of several pathological causes of degenerating motor neurons and is induced by activated microglial cells and astrocytes in ALS. Scolopendra subspinipes mutilans (SSM) is utilized in traditional Chinese and Korean medicine for the treatment of a variety of diseases, such as cancer, apoplexy, and epilepsy. However, the mechanisms underlying the effects of SSM are currently unclear, even though SSM increases immune and antibiotic activity. Methods To determine the effects of SSM on symptomatic hSOD1G93A transgenic mice, SSM (2.5 μℓ/g) was injected bilaterally at the Zusanli (ST36) acupoint three times per week for two weeks. The effects of SSM treatment on anti-neuroinflammation in the brainstem and spinal cord of hSOD1G93A mice were assessed via Nissl and Fluoro-Jade B (FJB) staining, and immunohistochemistry using Iba-1, CD14, HO1, and NQO1 proteins was evaluated by Western blotting. Results In this study, we investigated whether SSM affects neuroinflammation in the spinal cord of symptomatic hSOD1G93A transgenic mice. We found that SSM treatment attenuated the loss of motor neurons and reduced the activation of microglial cells and astrocytes. Furthermore, we demonstrated that SSM administration in this animal model of ALS suppressed oxidative stress in the brainstem and spinal cord by 1.6- and 1.8-fold, respectively. Conclusions Our findings suggest that SSM, which has previously been used in complementary and alternative medicine (CAM), might also be considered as an anti-neuroinflammatory therapy for neurodegenerative diseases.
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Affiliation(s)
| | | | | | | | - Sungchul Kim
- Department of Medial Research, Korea Institute of Oriental Medicine, 483 Expo-ro, Yuseong-gu, Daejeon 305-811, Republic of Korea.
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Kong Y, Shao Y, Chen H, Ming X, Wang JB, Li ZY, Wei JF. A Novel Factor Xa-Inhibiting Peptide from Centipedes Venom. Int J Pept Res Ther 2013; 19:303-311. [PMID: 24273471 PMCID: PMC3824214 DOI: 10.1007/s10989-013-9353-0] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/05/2013] [Indexed: 11/26/2022]
Abstract
Centipedes have been used as traditional medicine for thousands of years in China. Centipede venoms consist of many biochemical peptides and proteins. Factor Xa (FXa) is a serine endopeptidase that plays the key role in blood coagulation, and has been used as a new target for anti-thrombotic drug development. A novel FXa inhibitor, a natural peptide with the sequence of Thr-Asn-Gly-Tyr-Thr (TNGYT), was isolated from the venom of Scolopendra subspinipesmutilans using a combination of size-exclusion and reverse-phase chromatography. The molecular weight of the TNGYT peptide was 554.3 Da measured by electrospray ionization mass spectrometry. The amino acid sequence of TNGYT was determined by Edman degradation. TNGYT inhibited the activity of FXa in a dose-dependent manner with an IC50 value of 41.14 mg/ml. It prolonged the partial thromboplastin time and prothrombin time in both in vitro and ex vivo assays. It also significantly prolonged whole blood clotting time and bleeding time in mice. This is the first report that an FXa inhibiting peptide was isolated from centipedes venom.
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Affiliation(s)
- Yi Kong
- School of Life Science & Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009 People’s Republic of China
- State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009 People’s Republic of China
| | - Yu Shao
- School of Life Science & Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009 People’s Republic of China
| | - Hao Chen
- School of Life Science & Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009 People’s Republic of China
| | - Xin Ming
- Division of Molecular Pharmaceutics, UNC Eshelman School of Pharmacy, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599 USA
| | - Jin-Bin Wang
- School of Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009 People’s Republic of China
| | - Zhi-Yu Li
- School of Pharmacy, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing, 210009 People’s Republic of China
| | - Ji-Fu Wei
- Research Division of Clinical Pharmacology, The First Affiliated Hospital with Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029 China
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Jo IJ, Bae GS, Park KC, Choi SB, Jung WS, Jung SY, Cho JH, Choi MO, Song HJ, Park SJ. Scolopendra subspinipes mutilans protected the cerulein-induced acute pancreatitis by inhibiting high-mobility group box protein-1. World J Gastroenterol 2013; 19:1551-1562. [PMID: 23539679 PMCID: PMC3602472 DOI: 10.3748/wjg.v19.i10.1551] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2012] [Revised: 10/15/2012] [Accepted: 10/30/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To evaluate the inhibitory effects of Scolopendra subspinipes mutilans (SSM) on cerulein-induced acute pancreatitis (AP) in a mouse model.
METHODS: SSM water extract (0.1, 0.5, or 1 g/kg) was administrated intraperitoneally 1 h prior to the first injection of cerulein. Once AP developed, the stable cholecystokinin analogue, cerulein was injected hourly, over a 6 h period. Blood samples were taken 6 h later to determine serum amylase, lipase, and cytokine levels. The pancreas and lungs were rapidly removed for morphological examination, myeloperoxidase assay, and real-time reverse transcription polymerase chain reaction. To specify the role of SSM in pancreatitis, the pancreatic acinar cells were isolated using collagenase method. Then the cells were pre-treated with SSM, then stimulated with cerulein. The cell viability, cytokine productions and high-mobility group box protein-1 (HMGB-1) were measured. Furthermore, the regulating mechanisms of SSM action were evaluated.
RESULTS: The administration of SSM significantly attenuated the severity of pancreatitis and pancreatitis associated lung injury, as was shown by the reduction in pancreatic edema, neutrophil infiltration, vacuolization and necrosis. SSM treatment also reduced pancreatic weight/body weight ratio, serum amylase, lipase and cytokine levels, and mRNA expression of multiple inflammatory mediators such as tumor necrosis factor-α and interleukin-1β. In addition, treatment with SSM inhibited HMGB-1 expression in the pancreas during AP. In accordance with in vivo data, SSM inhibited the cerulein-induced acinar cell death, cytokine, and HMGB-1 release. SSM also inhibited the activation of c-Jun NH2-terminal kinase, p38 and nuclear factor (NF)-κB.
CONCLUSION: These results suggest that SSM plays a protective role during the development of AP and pancreatitis associated lung injury via deactivating c-Jun NH2-terminal kinase, p38 and NF-κB.
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Molecular cloning and functional expression of a fibrinolytic protease gene from the polychaeta, Periserrula leucophryna. BIOTECHNOL BIOPROC E 2013. [DOI: 10.1007/s12257-012-0800-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
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Kong Y, Huang SL, Shao Y, Li S, Wei JF. Purification and characterization of a novel antithrombotic peptide from Scolopendra subspinipes mutilans. JOURNAL OF ETHNOPHARMACOLOGY 2013; 145:182-186. [PMID: 23127646 DOI: 10.1016/j.jep.2012.10.048] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/12/2012] [Revised: 10/22/2012] [Accepted: 10/25/2012] [Indexed: 06/01/2023]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE The centipede has been prescribed for the treatment of cardiovascular diseases in Korea, China and other Far Eastern Asian countries for several hundred years. MATERIALS AND METHODS A novel antithrombotic peptide was isolated from Scolopendra subspinipes mutilans using a combination of ultrafiltration, Sephadex G-50 column, Source 15Q anion exchange column and RP-HPLC C18 column. RESULTS The molecular mass of the purified peptide is 346Da measured by Electrospray Ionization Mass Spectrometry (ESI-MS). The primary structure of the peptide is Ser-Gln-Leu (SQL) determined by Edman degradation. SQL potently prolonged the activated partial thromboplastin time (aPTT), and inhibited platelet aggregation. CONCLUSIONS These results help to clarify the mechanism of the antithrombotic activity of the centipede for effective treatment of cardiovascular and cerebrovascular diseases.
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Affiliation(s)
- Yi Kong
- School of Life Science & Technology, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, PR China.
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Liu ZC, Zhang R, Zhao F, Chen ZM, Liu HW, Wang YJ, Jiang P, Zhang Y, Wu Y, Ding JP, Lee WH, Zhang Y. Venomic and Transcriptomic Analysis of Centipede Scolopendra subspinipes dehaani. J Proteome Res 2012; 11:6197-212. [DOI: 10.1021/pr300881d] [Citation(s) in RCA: 66] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Affiliation(s)
- Zi-Chao Liu
- Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming, Yunnan 650223, China
- Graduate School of the Chinese Academy of Sciences, Beijing 100049, China
| | - Rong Zhang
- Key Laboratory of Molecular
Biophysics, Huazhong University of Science and Technology, the Ministry of Education, Wuhan, Hubei 430074, China
| | - Feng Zhao
- Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming, Yunnan 650223, China
- Graduate School of the Chinese Academy of Sciences, Beijing 100049, China
| | - Zhong-Ming Chen
- Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming, Yunnan 650223, China
| | - Hao-Wen Liu
- Key Laboratory of Molecular
Biophysics, Huazhong University of Science and Technology, the Ministry of Education, Wuhan, Hubei 430074, China
| | - Yan-Jie Wang
- Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming, Yunnan 650223, China
| | - Ping Jiang
- Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming, Yunnan 650223, China
| | - Yong Zhang
- Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming, Yunnan 650223, China
| | - Ying Wu
- Key Laboratory of Molecular
Biophysics, Huazhong University of Science and Technology, the Ministry of Education, Wuhan, Hubei 430074, China
| | - Jiu-Ping Ding
- Key Laboratory of Molecular
Biophysics, Huazhong University of Science and Technology, the Ministry of Education, Wuhan, Hubei 430074, China
| | - Wen-Hui Lee
- Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming, Yunnan 650223, China
| | - Yun Zhang
- Key Laboratory of Animal Models and Human Disease Mechanisms of Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming, Yunnan 650223, China
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Purification and characterization of a fibrinolytic enzyme from Streptomyces sp. XZNUM 00004. World J Microbiol Biotechnol 2012; 28:2479-86. [PMID: 22806153 DOI: 10.1007/s11274-012-1055-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2011] [Accepted: 04/09/2012] [Indexed: 10/28/2022]
Abstract
A fibrinolytic enzyme (SFE1) from Streptomyces sp. XZNUM 00004 was purified to electrophoretic homogeneity with the methods including ammonium sulfate precipitation, polyacrylamide gel, DEAE-Sepharose Fast Flow anion exchange and gel-filtration chromatography. The molecular weight of SFE1 was estimated to be 20 kDa by SDS-PAGE, fibrin zymography, and gel filtration chromatography. The isoelectric point was 4.9. K (m) and V (max) values were 0.96 mg/ml and 181.8 unit/ml, respectively. It was very stable at pH 5.0-8.0 and below 65 °C. The optimum pH for enzyme activity was 7.8. The optimum temperature was 35 °C. The fibrinolytic activity of SFE1 was enhanced by Na(+), K(+), Mn(2+), Mg(2+), Zn(2+) and Co(2+). Conversely, Cu(2+) showed strong inhibition. Furthermore, the fibrinolytic activity was strongly inhibited by PMSF, and partly inhibited by EDTA and EGTA. SFE1 rapidly hydrolyzed the Aα-chain of fibrinogen, followed by the Bβ-chain and finally the γ-chain. The first 15 amino acids of the N-terminal sequence were APITLSQGHVDVVDI. Additionally, SFE1 directly digested fibrin and not by plasminogen activators in vitro. SFE1 can be further developed as a potential candidate for thrombolytic therapy.
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Wang S, Deng Z, Li Q, Ge X, Bo Q, Liu J, Cui J, Jiang X, Liu J, Zhang L, Hong M. A novel alkaline serine protease with fibrinolytic activity from the polychaete, Neanthes japonica. Comp Biochem Physiol B Biochem Mol Biol 2011; 159:18-25. [PMID: 21276864 DOI: 10.1016/j.cbpb.2011.01.004] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2010] [Revised: 01/20/2011] [Accepted: 01/22/2011] [Indexed: 11/29/2022]
Abstract
A new protease named NJP with fibrinolytic activity was isolated from Neanthes japonica (Izuka), by a combination of ammonium sulfate fractionation, hydrophobic chromatography, ion-exchange chromatography and gel filtration. The molecular mass of NJP was approximately 28.6-33.5kDa as estimated by MALDI-TOF mass spectrometry and SDS-PAGE, which revealed a monomeric form of the protease. The isoelectric point of NJP determined by 2-DE was 9.2. NJP was stable in the range of pH 7.0-11.0 with a maximum enzymatic activity at 40°C and pH 9.0. The hydrolyzing activity of NJP on fibrinogen started from the Aα-chain, followed by the Bβ-chain, and the γ-chain at last. NJP had also a higher specificity for the chromogenic substrate S-2238 for thrombin. NJP activity was completely inhibited by PMSF. Analysis of partial amino acid sequences showed that NJP had very low homology with other known fibrinolytic enzymes. These results indicate that NJP is a novel alkaline thrombin-like serine protease. Thus NJP may have potential applications in the prevention and treatment of thrombosis.
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Affiliation(s)
- Shaohua Wang
- Department of Biochemistry and Molecular Biology, Norman Bethune College of Medicine, Jilin University, 126 Xinmin Street, Changchun, Jilin, China
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González-Morales L, Diego-García E, Segovia L, Carmen Gutiérrez MD, Possani LD. Venom from the centipede Scolopendra viridis Say: Purification, gene cloning and phylogenetic analysis of a phospholipase A2. Toxicon 2009; 54:8-15. [DOI: 10.1016/j.toxicon.2009.03.003] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2008] [Revised: 02/18/2009] [Accepted: 03/02/2009] [Indexed: 11/15/2022]
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Wang D, Liu W, Han B, Xu R. Biochemical and enzymatic properties of a novel marine fibrinolytic enzyme from Urechis unicinctus. Appl Biochem Biotechnol 2007; 136:251-64. [PMID: 17625232 DOI: 10.1007/s12010-007-9024-8] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2005] [Revised: 05/09/2006] [Accepted: 05/25/2006] [Indexed: 11/27/2022]
Abstract
A novel potent protease, Urechis unicinctus fibrinolytic enzyme (UFE), was first discovered by our laboratory. In this study, we further investigated the enzymatic properties and dynamic parameters of UFE. As a low molecular weight protein, UFE appeared to be very stable to heat and pH. When the temperature was <50 degrees C, the remnant enzyme activity remained almost unchanged, but when the temperature was raised to 60 degrees C the remnant enzyme activity began to decrease rapidly. UFE was quite stable in a pH range of 3.0-12.0, especially at slightly alkaline pH values. Mn(2+), Cu(2+), and Fe(2+) ions were activators of UFE, whereas Fe(3+) and Ag(+) ions were inhibitors. Fe(2+) ion along with Fe(3+) ion might regulate UFE activity in vivo. The optimum pH and temperature of UFE were about 8.0 and 50 degrees C, respectively. When using casein as substrate and a substrate concentration <0.1% casein (w/v), the reaction velocity was increased with substrate concentration. Also when using casein as substrate, the determined K(m) and V(max) of UFE were 0.5298 mg/mL and 3.0845 mol of L-tyrosine equivalent, respectively. Our systematic research results are significant when UFE is applied for medical and industrial purposes.
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Affiliation(s)
- Dianliang Wang
- College of Marine Life Sciences, Ocean University of China, Qingdao, China.
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Yoo YC, Shin BH, Hong JH, Lee J, Chee HY, Song KS, Lee KB. Isolation of fatty acids with anticancer activity from Protaetia brevitarsis larva. Arch Pharm Res 2007; 30:361-5. [PMID: 17424944 DOI: 10.1007/bf02977619] [Citation(s) in RCA: 63] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
In this study, biologically active compounds were isolated from Protaetia brevitarsis larva (PBL) by dichloromethane extraction. The dichloromethane extract from PBL was highly cytotoxic to various cancer cells. From a silica gel column chromatograpy of this extract, we obtained four fractions (F-2, F-4, F-5 and F-7) having apoptosis-inducing activity. These fractions induced DNA ladder and caspase-3 activation during apoptosis in colon 26 tumor cells. In 1H and 13C NMR and mass spectral analysis of the fraction F-2 showing the highest apoptosis-inducing activity, we found that the fraction was composed of three free fatty acids such as palmitic acid, (Z)-9-octadecenoic acid and octadecenoic acid. These results indicate that the dichloromethane extract of PBL includes anticancer components composed of at least three fatty acids, and apoptosis-inducing activity of the extract was mediated by caspase-3 activation in tumor cells.
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Affiliation(s)
- Yung-Choon Yoo
- Department of Biochemistry, College of Medicine, Konyang University, Daejeon 302-801, Korea
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Rates B, Bemquerer MP, Richardson M, Borges MH, Morales RAV, De Lima ME, Pimenta AMC. Venomic analyses of Scolopendra viridicornis nigra and Scolopendra angulata (Centipede, Scolopendromorpha): Shedding light on venoms from a neglected group. Toxicon 2007; 49:810-26. [PMID: 17320133 DOI: 10.1016/j.toxicon.2006.12.001] [Citation(s) in RCA: 48] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2006] [Revised: 12/01/2006] [Accepted: 12/11/2006] [Indexed: 11/29/2022]
Abstract
Centipedes are venomous arthropods responsible for a significant number of non-lethal human envenomations. Despite this, information about the composition and function of their venom contents is scarce. In this study, we have used a 'structure to function' proteomic approach combining two-dimensional chromatography (2D-LC), electrospray ionization quadrupole/time-of-flight mass spectrometry (ESI-Q-TOF/MS), N-terminal sequencing and similarity searching to better understand the complexities of the venoms from two Brazilian centipede species: Scolopendra viridicornis nigra and Scolopendra angulata. Comparisons between the LC profiles and the mass compositions of the venoms of the two species are provided. The observed molecular masses ranged from 3019.62 to 20996.94Da in S. viridicornis nigra (total: 62 molecular masses) and from 1304.73 to 22639.15Da in S. angulata (total: 65 molecular masses). Also, the N-termini of representatives of 10 protein/peptide families were successfully sequenced where nine of them showed no significant similarity to other protein sequences deposited in the Swiss-Prot database. A screening for insecto-toxic activities in fractions from S. viridicornis venom has also been performed. Six out of the 12 tested fractions were responsible for clear toxic effects in house flies. This work demonstrates that centipede venoms might be a neglected but important source of new bioactive compounds.
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Affiliation(s)
- Breno Rates
- Departamento de Bioquímica e Imunologia, Laboratório de Venenos e Toxinas Animais, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
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Wang CT, Ji BP, Li B, Nout R, Li PL, Ji H, Chen LF. Purification and characterization of a fibrinolytic enzyme of Bacillus subtilis DC33, isolated from Chinese traditional Douchi. J Ind Microbiol Biotechnol 2006; 33:750-8. [PMID: 16575557 DOI: 10.1007/s10295-006-0111-6] [Citation(s) in RCA: 103] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2005] [Accepted: 02/08/2006] [Indexed: 12/01/2022]
Abstract
Bacillus subtilis DC33 producing a novel fibrinolytic enzyme was isolated from Ba-bao Douchi, a traditional soybean-fermented food in China. The strong fibrin-specific enzyme subtilisin FS33 was purified to electrophoretic homogeneity using the combination of various chromatographic steps. The optimum temperature, pH value, and pI of subtilisin FS33 were 55 degrees C, 8.0, and 8.7, respectively. The molecular weight was 30 kDa measured by SDS-PAGE under both reducing and non-reducing conditions. The enzyme showed a level of fibrinolytic activity that was about six times higher than that of subtilisin Carlsberg. The first 15 amino acid residues of N-terminal sequence of the enzyme were A-Q-S-V-P-Y-G-I-P-Q-I-K-A-P-A, which are different from that of other known fibrinolytic enzymes. The amidolytic activities of subtilisin FS33 were inhibited completely by 5 mM phenylmethanesulfonyl fluoride (PMSF) and 1 mM soybean trypsin inhibitor (SBTI), but 1,4-dithiothreitol (DTT), beta-mercaptoethanol, and p-hydroxymercuribenzoate (PHMB) did not affect the enzyme activity; serine and tryptophan are thus essential in the active site of the enzyme. The highest affinity of subtilisin FS33 was towards N-Succ-Ala-Ala-Pro-Phe-pNA. Therefore, the enzyme was considered to be a subtilisin-like serine protease. The fibrinolytic enzyme had a high degrading activity for the Bbeta-chains and Aalpha-chain of fibrin(ogen), and also acted on thrombotic and fibrinolytic factors of blood, such as plasminogen, urokinase, thrombin, and kallikrein. So subtilisin FS33 was able to degrade fibrin clots in two ways, i.e., (a) by forming active plasmin from plasminogen and (b) by direct fibrinolysis.
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Affiliation(s)
- Cheng Tao Wang
- College of Food Science and Nutritional Engineering, China Agricultural University, East Campus, Beijing, China
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Vaseeharan B, Lin YC, Ko CF, Chen JC. Cloning and characterisation of a serine proteinase from the haemocytes of mud crab Scylla serrata. FISH & SHELLFISH IMMUNOLOGY 2006; 21:20-31. [PMID: 16326112 DOI: 10.1016/j.fsi.2005.09.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/02/2005] [Revised: 09/09/2005] [Accepted: 09/27/2005] [Indexed: 05/05/2023]
Abstract
A serine proteinase (SP) cDNA was cloned from the haemocytes of mud crab Scylla serrata using oligonucleotide primers and RT-PCR. Both 3'- and 5'-regions were isolated by rapid amplification of cDNA end (RACE) method. Analysis of the nucleotide sequence revealed that the cDNA clone has an open reading frame of 1,131 bp encoding a protein of 376 amino acids. The calculated molecular mass of the SP mature protein is 39.54 kDa with an estimated pI of 5.37. The C-terminal half of S. serrata SP is composed of a trypsin-like domain, with a sequence similar to that of other invertebrate and vertebrate SP domain. The typical catalytic triad of SP required for functional activity (His150, Asp217 and Ser331) was conserved in the polypeptide sequence. Sequence comparison showed that SP deduced amino acid has an overall similarity of 55%, 51% and 50% to SP deduced amino acid from spiny lobster Panulirus argus, horseshoe crab Tachypleus tridentatus and crayfish Pacifastaus leniusculus, respectively. The SP was strongly expressed in haemocytes, but was weakly expressed in heart, eyestalk and antennules. The SP transcript decreased significantly for the S. serrata following 3 days exposure to pH 9.5. However, the SP transcript increased significantly 24 h post-zymosan injection.
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Affiliation(s)
- Baskaralingam Vaseeharan
- Department of Aquaculture, College of Life Sciences, National Taiwan Ocean University, No: 2 Pei-Ning Road, Keelung 202, Taiwan, ROC
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