HepG2细胞中TNFα通过NF-κB信号通路下调GSTA1/GSTA4表达（英文）

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

谷胱甘肽巯基转移酶α1/α4(GSTA1/A4)是体内重要的解毒酶,可降低多种内、外源性毒性化合物的毒性.然而,胆汁淤积病人肝细胞内G STA1/A4的表达是下调的,下调机制尚不清楚.本研究通过肿瘤坏死因子α(TNFα)处理人肝癌细胞Hep G2细胞,利用实时荧光定量聚合酶链式反应(q PCR)和蛋白质印迹(Western blot)检测GSTA1/A4、核因子κB(NF-κB)和核因子E2相关因子2(Nrf2)的表达.发现TNFα在m RNA水平和蛋白质水平均抑制GSTA1/A4表达,且呈剂量与时间依赖关系.干扰NF-κB信号通路,可减弱T NFα对G STA1/A4表达的抑制作用.以上结果表明,在Hep G2细胞中,TNFα可通过激活N F-κB信号通路抑制G STA1/A4表达.

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 Hep G2 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（q PCR） and Western blotting.We found that expression of GSTA1/4 was repressed by TNFα at both the m RNA 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 Hep G2 cells.Our findings indicate that down-regulation of GSTA1/4 expression in Hep G2 cells is likely triggered by TNFα and mediated by activation of the NF-κB signaling pathway.