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

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.