Crosstalk Between the Mitochondrial Dynamics and Oxidative Stress in Zinc-induced Cytotoxicity

文献类型： 外文期刊

第一作者： Yang, Qingwen

作者： Yang, Qingwen;Zhang, Yi;Yong, Kang;Yang, Junjie;Liu, Xuesong;Zhong, Peng;Li, Yue;Ao, Da

作者机构：

关键词： Zinc; Mitochondrial dynamics; Oxidative stress; Cytotoxicity

期刊名称：BIOLOGICAL TRACE ELEMENT RESEARCH （ 影响因子：4.081； 五年影响因子：3.755 ）

ISSN： 0163-4984

年卷期：

页码：

收录情况： SCI

摘要： Zinc is an essential trace element, which plays an important role in multiple biological activities. However, excessive exposure to zinc can cause toxic damage to living organism. Here, we investigated the relationship between oxidative stress and mitochondrial dynamics in the zinc-induced cytotoxicity. Results showed that excess exposure to zinc could significantly reduce cell viability and induce cell vacuolation in PK-15 cells. Additionally, zinc exposure caused mitochondrial dynamics disorder, manifested as mitochondrial fission, and the elevated mRNA level of Drp1 and downregulated mRNA levels of OPA1, Mfn1, and Mfn2. Meanwhile, zinc could induce oxidative damage, evidenced by the increasing levels of hydrogen peroxide, malondialdehyde, lipid peroxidation, oxidized form of nicotinamide adenine dinucleotide phosphate/nicotinamide adenine dinucleotide phosphate, oxidized glutathione/glutathione, superoxide dismutase activity, and the mRNA expression of SOD-1 and NOQ1, and decreasing levels of catalase activity, glutathione peroxidase activity, glutathione reductase activity, and the mRNA expression of CAT, and GPX1. Interestingly, N-acetyl-L-cysteine, an inhibitor for oxidative stress, could reduce the mitochondrial fission under zinc treatment. Besides, Mdivi-1, a mitochondrial fission inhibitor, could relieve oxidative stress caused by excess zinc. In general, these results suggested that mitochondrial fission and oxidative stress induced by zinc were interrelated in PK-15 cells, which is conducive to explore the new mechanism of zinc toxicity and proposes a theoretical foundation for selecting effective drugs to alleviate the toxic effects caused by zinc.

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