The role of mitochondrial dynamics imbalance in hexavalent chromium-induced apoptosis and autophagy in rat testis

文献类型: 外文期刊

第一作者: Wang, Ruonan

作者: Wang, Ruonan;Yu, Lu;Li, Siyu;Li, Jiayi;Han, Biqi;Zheng, Xiaoyan;Zhang, Zhigang;Huang, Yuxiang

作者机构:

关键词: Cr(VI); Mitochondrial dynamics; Apoptosis; Autophagy; Oxidative stress; Testicular toxicity

期刊名称:CHEMICO-BIOLOGICAL INTERACTIONS ( 影响因子:5.1; 五年影响因子:4.9 )

ISSN: 0009-2797

年卷期: 2023 年 374 卷

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收录情况: SCI

摘要: Hexavalent chromium (Cr(VI)) is a ubiquitous environmental pollutant that can cause reproductive toxicity. However, the exact mechanism of Cr(VI)-induced testis toxicity remains largely elusive. This study aims to explore the possible molecular mechanism of Cr(VI)-provoked testicular toxicity. Male Wistar rats were intra-peritoneally injected with 0, 2, 4, or 6 mg/kg body weight/day of potassium dichromate (K2Cr2O7), respectively, for 5 weeks. The results revealed that Cr(VI)-treated rat testis presented varying degrees of damage in a dose-dependent manner. Concretely, Cr(VI) administration suppressed Sirtuin 1/Peroxisome proliferator-activated receptor-gamma coactivator-1 alpha pathway and led to mitochondrial dynamics disorder, along with the elevation of mitochondrial division and the repression of mitochondrial fusion. Meanwhile, the downstream effector of Sirt1, nuclear factor-erythroid-2-related factor 2 (Nrf2), was downregulated, and correspondingly exacerbated oxida-tive stress. Mitochondrial dynamics disorder and Nrf2 inhibition collectively contribute to abnormal mito-chondrial dynamics in testis, which further promotes apoptosis and autophagy, evidenced by dose-dependently increasing the protein levels and gene expressions of apoptosis-related (including Bcl-2-associated X protein, cytochrome c, and cleaved-caspase 3) and autophagy-related (Beclin-1, ATG4B, and ATG5). Collectively, our results demonstrate that Cr(VI) exposure induced testis apoptosis and autophagy by disrupting the balance of mitochondrial dynamics and the oxidation-reduction process in rats.

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