Tumor Necrosis Factor Alpha Down-regulated Human GSTA1 and GSTA4 Expression Through The NF-κB Signaling Pathway in Human Hepatoma HepG2 Cells

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Tumor Necrosis Factor Alpha Down-regulated Human GSTA1 and GSTA4 Expression Through The NF-κB Signaling Pathway in Human Hepatoma HepG2 Cells
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Affiliation:Cholestatic Liver Diseases Center, Institute of Gastroenterology of P.L.A., Southwest Hospital, Third Military Medical University,Cholestatic Liver Diseases Center, Institute of Gastroenterology of P.L.A., Southwest Hospital, Third Military Medical University,Cholestatic Liver Diseases Center, Institute of Gastroenterology of P.L.A., Southwest Hospital, Third Military Medical University,Cholestatic Liver Diseases Center, Institute of Gastroenterology of P.L.A., Southwest Hospital, Third Military Medical University,Cholestatic Liver Diseases Center, Institute of Gastroenterology of P.L.A., Southwest Hospital, Third Military Medical University,Cholestatic Liver Diseases Center, Institute of Gastroenterology of P.L.A., Southwest Hospital, Third Military Medical University,Cholestatic Liver Diseases Center, Institute of Gastroenterology of P.L.A., Southwest Hospital, Third Military Medical University,Cholestatic Liver Diseases Center, Institute of Gastroenterology of P.L.A., Southwest Hospital, Third Military Medical University
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Fund Project:This work was supported by grants from The National Natural Science Foundation of China (81370560, 81570576, 81470850, 81470880)

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Abstract:

Glutathione S-transferase Alpha1 and Alpha 4 (GSTA1 and GSTA4) are crucial for detoxifying a variety of endogenous and exogenous toxic compounds. However, GSTA1/4 expression is reduced in cholestatic patients. The molecular mechanism of GSTA1/4 down-regulation remains elusive. Here, we treated human hepatoma HepG2 cells with tumor necrosis factor alpha (TNFα) and measured the expression of GSTA1/4, nuclear factor kappa B (NF-κB) and NF-E2 related factor 2 (Nrf2) by quantitative real-time quantitative polymerase chain reaction (qPCR) and Western blotting. We found that expression of GSTA1/4 was repressed by TNFα at both the mRNA and the protein level in a dose- and time-dependent manner. Furthermore, inhibiting the NF-κB signaling pathway could attenuate the TNFα induced reduction in GSTA1/4 expression in the HepG2 cells. Our findings indicate that down-regulation of GSTA1/4 expression in HepG2 cells is likely triggered by TNFα and mediated by activation of the NF-κB signaling pathway.

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YANG Long, XIONG Zhi-Yong, ZHANG Liang-Jun, FENG Xin-Chan, CHEN Kun, LI Yan, CHENG Ying, LONG Qing-Lin, XIAO Tian-Li, CHEN Lei, YAN Wen-Hui, LI Ling-Xin, CHAI Jin, CHEN Wen-Sheng. Tumor Necrosis Factor Alpha Down-regulated Human GSTA1 and GSTA4 Expression Through The NF-κB Signaling Pathway in Human Hepatoma HepG2 Cells[J]. Progress in Biochemistry and Biophysics,2016,43(8):801-809

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Received:March 10,2016
Revised:May 25,2016
Accepted:June 16,2016
Online: August 05,2016
Published: August 20,2016

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