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.

Abstract:

AIM:To examine the potency of 1,2,3,4,6-penta-O-galloyl-beta-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.

journal_name

World J Gastroenterol

authors

Pae HO,Oh GS,Jeong SO,Jeong GS,Lee BS,Choi BM,Lee HS,Chung HT

doi

10.3748/wjg.v12.i2.214

keywords:

subject

Has Abstract

pub_date

2006-01-14 00:00:00

pages

214-21

issue

2

eissn

1007-9327

issn

2219-2840

journal_volume

12

pub_type

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