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无机汞暴露对肾细胞的有害影响:线粒体动力学紊乱与过度氧化应激

Harmful Effects of Inorganic Mercury Exposure on Kidney Cells: Mitochondrial Dynamics Disorder and Excessive Oxidative Stress.

作者信息

Han Biqi, Lv Zhanjun, Han Xuemin, Li Siyu, Han Bing, Yang Qingyue, Wang Xiaoqiao, Wu Pengfei, Li Jiayi, Deng Ning, Zhang Zhigang

机构信息

College of Veterinary Medicine, Northeast Agricultural University, No. 600 Changjiang Road, Harbin, 150030, China.

Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, 600 Changjiang Road, Harbin, 150030, China.

出版信息

Biol Trace Elem Res. 2022 Apr;200(4):1591-1597. doi: 10.1007/s12011-021-02766-3. Epub 2021 May 31.

DOI:10.1007/s12011-021-02766-3
PMID:34060062
Abstract

Mercury is widely used in industry and has caused global environmental pollution. Inorganic mercury accumulates in the body causes damage to many organs, and the kidney is the most susceptible to the toxic effects of mercury. However, the underlying specific molecular mechanism of renal injury induced by inorganic mercury remains unclear at the cellular level. Therefore, in order to understand its molecular mechanism, we used in vitro method. We established experimental models by treating human embryonic kidney epithelial cell line (HEK-293 T) cells with HgCl (0, 1.25, 5, and 20 µmol/L). We found that HgCl can lead to a decrease in cell viability and oxidative stress of HEK-293 T, which may be mediated by upregulation mitochondrial fission. In addition, HgCl exposure resulted in the mitochondrial disorder of HEK-293 T cells, which was mediated by downregulating the expression of silent information regulator two ortholog 1 (Sirt1)/peroxisome proliferator-activated receptor coactivator-1α (PGC-1α) signaling pathway. In summary, our results suggest that HgCl induces HEK-293 T cell toxicity through promoting Sirt1/PGC-1α axis-mediated mitochondrial dynamics disorder and oxidative stress. Sirt1/PGC-1α may be an appealing pharmaceutical target curing HgCl-induced kidney injury.

摘要

汞在工业中被广泛使用,并已造成全球环境污染。无机汞在体内蓄积会对许多器官造成损害,而肾脏是最易受汞毒性影响的器官。然而,无机汞诱导肾损伤的潜在具体分子机制在细胞水平上仍不清楚。因此,为了了解其分子机制,我们采用了体外方法。我们通过用HgCl(0、1.25、5和20µmol/L)处理人胚肾上皮细胞系(HEK-293 T)细胞建立了实验模型。我们发现HgCl可导致HEK-293 T细胞活力下降和氧化应激,这可能是由线粒体分裂上调介导的。此外,HgCl暴露导致HEK-293 T细胞线粒体紊乱,这是由沉默信息调节因子2同源物1(Sirt1)/过氧化物酶体增殖物激活受体共激活因子-1α(PGC-1α)信号通路表达下调介导的。总之,我们的结果表明,HgCl通过促进Sirt1/PGC-1α轴介导的线粒体动力学紊乱和氧化应激诱导HEK-293 T细胞毒性。Sirt1/PGC-1α可能是治疗HgCl诱导的肾损伤的一个有吸引力的药物靶点。

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