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 kinasedependent manner in HepG2 cells

• Published in: World journal of gastroenterology : WJG Vol. 12; no. 2; pp. 214 - 221
• Main Author: Hyun-Ock Pae Gi-Su Oh Sun-Oh Jeong Gil-Saeng Jeong Bok-Soo Lee Byung-Min Choi Ho-Sub Lee Hun-Taeg Chung
• Format: Journal Article
• Language: English
• Published: 2006
• Subjects: 三羟苯甲酰; 氧化压力; 葡萄糖; 血红素加氧酶
• ISSN: 1007-9327; 2219-2840

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 signalregulated 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.