1,2,3,4,6-penta-O-galloyl-&beta;-D-glucose up-regulates heme oxygenase-1 expression by stimulating Nrf2 nuclear translocation in an extracellular signal-regulated kinase-dependent manner in HepG2 cells

doi:10.3748/wjg.v12.i2.214

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. Jan 14, 2006; 12(2): 214-221
Published online Jan 14, 2006. doi: 10.3748/wjg.v12.i2.214

1,2,3,4,6-penta-O-galloyl-β-D-glucose up-regulates heme oxygenase-1 expression by stimulating Nrf2 nuclear translocation in an extracellular signal-regulated kinase-dependent manner in HepG2 cells

Hyun-Ock Pae, Gi-Su Oh, Sun-Oh Jeong, Gil-Saeng Jeong, Bok-Soo Lee, Byung-Min Choi, Ho-Sub Lee, Hun-Taeg Chung

Hyun-Ock Pae, Gi-Su Oh, Gil-Saeng Jeong, Bok-Soo Lee, Ho-Sub Lee, Hun-Taeg Chung, Medicinal Resources Research Institute, Wonkwang University, Iksan-Shi, Chunbug, 570-749, Republic of Korea

Sun-Oh Jeong, Byung-Min Choi, Department of Microbiology and Immunology, Wonkwang University School of Medicine, Wonkwang University, Iksan-Shi, Chunbug, 570-749, Republic of Korea

Co-first-author: Gi-Su Oh

Supported by the Korean Research Foundation Grant (KRF-2004-005-200038)

Correspondence to: Professor Hun-Taeg Chung, Department of Microbiology and Immunology, Wonkwang University School of Medicine, 344-2 Shinyoung-Dong, Iksan-Shi, Chonbug, 570-749, Republic of Korea. htchung@wonkwang.ac.kr

Telephone: +82-63-850-6762 Fax: +82-63-851-5066

Received: May 9, 2005
Revised: May 28, 2005
Accepted: June 2, 2005
Published online: January 14, 2006

Abstract

AIM: To examine the potency of 1,2,3,4,6-penta-O-galloyl-β-D-glucose (PGG) as a hepatic heme oxygenase-1 (HO-1) inducer and its regulation in HepG2 cells.

METHODS: Expression of HO-1 and NF-E2-related factor 2 (Nrf2) and activation of mitogen-activated protein (MAP) kinases were analyzed by Western blot, immunofluorescence assay, and flow cytometry. Transfections of HO-1 gene, small interfering RNAs for HO-1 and Nrf2, and dominant-negative gene for MAP/extracellular signal-regulated kinase (ERK) were carried out to dissect the signaling pathways leading to HO-1 expression in HepG 2 cells.

RESULTS: PGG up-regulated HO-1 expression and this expression conferred cytoprotection against oxidative injury induced by t-butyl hydroperoxide. Moreover, PGG induced Nrf2 nuclear translocation, which was found to be an upstream step of PGG-induced HO-1 expression, and ERK activation, of which pathway was involved in PGG-induced Nrf2 nuclear translocation, HO-1 expression and cytoprotection.

CONCLUSION: PGG up-regulates HO-1 expression by stimulating Nrf2 nuclear translocation in an ERK-dependent manner, and HO-1 expression by PGG may serve as one of the important mechanisms for its hepatoprotective effects.

Keywords: 1,2,3,4,6-penta-O-galloyl-β-D-glucose, Heme oxygenase-1, Oxidative stress, Hepatoprotection