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Essential roles of ERKs and p38K in up-regulation of GST A1 expression by Maotai content in human hepatoma cell line Hep3B

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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.

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Abbreviations

ARE:

anti-oxidant responsive element

ERKs:

extracellular signal regulated kinases

FBS:

fetal bovine serum

GST:

glutathione S-transferase

JNKs:

c-Jun N-terminal kinases

MAPKs:

mitogen activating protein kinases

MEM:

Eagle's Minimal Essential Medium

NFκB:

nuclear factor kappa B

MRWE:

Maotai residue without ethanol

Nrf-2:

nuclear factor E2 p45-related factor 2

p38 K:

p38 MAP kinase

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  1. Nelson Institute of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, New York, NY, 10987, USA

    Dongyun Zhang, Haitian Lu, Jingxia Li, Xianglin Shi & Chuanshu Huang

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Correspondence to Chuanshu Huang.

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Zhang, D., Lu, H., Li, J. et al. Essential roles of ERKs and p38K in up-regulation of GST A1 expression by Maotai content in human hepatoma cell line Hep3B. Mol Cell Biochem 293, 161–171 (2006). https://doi.org/10.1007/s11010-006-9238-z

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