Basic Research
Copyright ©The Author(s) 2004. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 15, 2004; 10(12): 1789-1794
Published online Jun 15, 2004. doi: 10.3748/wjg.v10.i12.1789
Heme oxygenase-1 in cholecystokinin-octapeptipe attenuated injury of pulmonary artery smooth muscle cells induced by lipopolysaccharide and its signal transduction mechanism
Xin-Li Huang, Yi-Ling Ling, Yi-Qun Ling, Jun-Lin Zhou, Yan Liu, Qiu-Hong Wang
Xin-Li Huang, Yi-Ling Ling, Qiu-Hong Wang, Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, Hebei province, China
Yi-Qun Ling, Department of Universal Surgery of Second Hospital, Hebei Medical University, Shijiazhuang 050017, Hebei Province, China
Jun-Lin Zhou, Department of hand Surgery of third Hospital, Hebei Medical University, Shijiazhuang 050017, Hebei province, China
Yan Liu, Department of histogy and embryology, Hebei Medical University, Shijiazhuang 050017, Hebei province, China
Author contributions: All authors contributed equally to the work.
Correspondence to: Professor Yi-Ling Ling, Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, Hebei province, China. lingyl20@sina.com.cn
Telephone: +86-311-6052263
Received: July 17, 2003
Revised: July 23, 2003
Accepted: July 30, 2003
Published online: June 15, 2004
Abstract

AIM: To study the effect of cholecystokinin-octapeptide (CCK-8) on lipopolysaccharide (LPS) -induced pulmonary artery smooth muscle cell (PASMCs) injury and the role of heme oxygenase-1 (HO-1), and to explore the regulation mechanism of c-Jun N-terminal kinase (JNK) and activator protein-1 (AP-1) signal transduction pathway in inducing HO-1 expression further.

METHODS: Cultured PASMCs were randomly divided into 4 or 6 groups: normal culture group, LPS (10 mg/L), CCK-8 (10-6 mol/L) plus LPS (10 mg/L) group, CCK-8 (10-6 mol/L) group, zinc protoporphyrin 9 (ZnPPIX) (10- 6 mol/L) plus LPS (10 mg/L) group, CCK-8 (10-6 mol/L) plus ZnPPIX and LPS (10 mg/L) group. Seven hours after LPS administration, ulterstructrual changes and content of malondialdehyde (MDA) of PASMCs in each group were investigated by electron microscopy and biochemical assay respectively. HO-1 mRNA and protein of PASMCs in the former4 groups were examined by reverse transcriptase polymerase chain reaction (RT-PCR) and immunocytochemistry staining. Changes of c-fos expression and activation of JNK of PASMCs in the former 4 groups were detected with immunocytochemistry staining and Western blot 30 min after LPS administration.

RESULTS: The injuries of PASMCs and the increases of MDA content induced by LPS were alleviated and significantly reduced by CCK-8 (P < 0.05). The specific HO-1 inhibitor-ZnPPIX could worsen LPS-induced injuries and weaken the protective effect of CCK-8. The expressions of c-fos, p-JNK protein and HO-1 mRNA and protein were all slightly increased in LPS group, and significantly enhanced by CCK-8 further (P < 0.05).

CONCLUSION: HO-1 may be a key factor in CCK-8 attenuated injuries of PASMCs induced by LPS, and HO-1 expression may be related to the activation of JNK and activator protein (AP-1).

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