title: Essential roles of ERKs and p38K in up-regulation of GST A1 expression by Maotai content in human hepatoma cell line Hep3B.
abstract: It is widely accepted that the consumption of alcohol may lead to hepatic injuries such as hepatic fibrosis and cirrhosis. However, consumption of Maotai, one of the famous liquors in China, is found to have no obvious relevance with hepatic injury as ordinary white wine does in both epidemiological and histopathological studies. Present study used human hepatoma cell line Hep3B to address the mechanisms involved in the resistance of alcohol-induced hepatic injury by Maotai liquor. We found that exposure of Hep3B cells to Maotai residue without ethanol (MRWE) resulted in the increased GST A1 anti-oxidant responsive element (ARE) transcriptional expression, while MRWE treatment did not affect Nrf-2-dependent transcriptional activity. Those findings were further confirmed at all time points and doses tested, suggesting that GST A1 transcription was regulated by MRWE via an Nrf-2-independent pathway. Consistent with GST A1 induction, the phosphorylation of c-Jun, extracellular signal-regulated kinases (ERKs) and p38 kinase (p38 K), were also observed in MRWE-treated Hep3B cells. Furthermore, pretreatment of cells with either PD98059 (an inhibitor specific for MEK1/2-ERKs pathway) or SB202190 (an inhibitor specific for p38 K) led to a significant decrease in the induction of GST A1 transcriptional expression by MRWE treatment. Our results indicate that certain content in MRWE is able to induce GST A1 ARE transcriptional expression, which may provide protective effects for hepatic cells by antagonizing the oxidative stress derived from ethanol via an ERKs- and p38 K-dependent pathway.
authors.affiliation: Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA.
authors.forename: Dongyun
authors.initials: D
authors.lastname: Zhang
authors.forename: Haitian
authors.initials: H
authors.lastname: Lu
authors.forename: Jingxia
authors.initials: J
authors.lastname: Li
authors.forename: Xianglin
authors.initials: X
authors.lastname: Shi
authors.forename: Chuanshu
authors.initials: C
authors.lastname: Huang
mesh_terms: D000434:Alcoholic Beverages; D006528:Carcinoma, Hepatocellular; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005982:Glutathione Transferase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000201:enzymology*; D008113:Liver Neoplasms; D008954:Models, Biological; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015854:Up-Regulation; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D048049:Extracellular Signal-Regulated MAP Kinases; D005982:Glutathione Transferase; D051267:NF-E2-Related Factor 2; D017346:Protein Serine-Threonine Kinases; D018808:Transcription Factor AP-1; D048051:p38 Mitogen-Activated Protein Kinases; D000097782:NF-kappaB-Inducing Kinase; C495635:NFE2L2 protein, human; C484555:GSTA1 protein, human