Drp1-dependent mitochondrial fission contributes to Cr(VI)-induced mitophagy and hepatotoxicity.
Drp1-dependent mitochondrial fission contributes to Cr(VI)-induced mitophagy and hepatotoxicity.
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Drp1 依赖性线粒体分裂有助于 Cr(VI) 诱导的线粒体自噬和肝毒性。
DOI：
10.1016/j.ecoenv.2020.110928
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发表时间：
2020-10
影响因子：
6.8
通讯作者：
Xiao Fang
中科院分区：
文献类型：
--
作者：
Zhang Yujing;Ma Yu;Xiao Yuanyuan;Lu Chan;Xiao Fang
六价铬[Cr（VI）]具有很强的毒性，对生态系统和生物体危害严重。动力蛋白相关蛋白1（Drp 1）和Drp 1相关的线粒体片段化在Cr（VI）暴露后的线粒体自噬和细胞毒性中的作用至今尚未阐明。我们证实，铬（VI）引起线粒体分裂上调Drp 1的表达和增强Drp 1线粒体易位。通过应用细胞内Ca ~（2+）拮抗剂BAPTA-AM和线粒体Ca ~（2+）拮抗剂Ru 360，我们证明了Cr（VI）诱导的线粒体过度分裂是以Ca ~（2+）-Drp 1依赖的方式进行的。Drp 1 siRNA的施用显著抑制Cr（VI）诱导的肝毒性中线粒体自噬的过度活化。特异性Drp 1抑制剂线粒体分裂抑制剂-1（Mdivi-1）阻断了过度活跃的线粒体自噬，随后改善了Cr（VI）在体内引起的肝毒性。结论：Cr（VI）诱导的线粒体自噬和肝毒性可能与Drp 1依赖的线粒体分裂有关，这为研究铬相关毒性，特别是预防铬暴露人群的健康损害提供了实验依据。
Hexavalent chromium [Cr(VI)] is seriously harmful to ecosystems and living organisms due to its strong toxicity. Role of dynamin-related protein 1 (Drp1) and Drp1-associated mitochondrial fragmentation in mitophagy and cytotoxicity after Cr(VI) exposure has not been clarified so far. We confirmed that Cr(VI) caused mitochondrial fission by up-regulating Drp1 expression and enhancing Drp1 mitochondrial translocation. By applying the intracellular Ca2+antagonist BAPTA-AM and mitochondrial Ca2+antagonist Ru360, we demonstrated that Cr(VI)-induced excessive mitochondrial fission was in a Ca2+-Drp1 dependent manner. The administration of Drp1 siRNA significantly suppressed the overactivation of mitophagy in Cr(VI)-induced hepatotoxicity. The specific Drp1 inhibitor mitochondrial division inhibitor-1 (Mdivi-1) blocked the overactive mitophagy and subsequently ameliorated hepatotoxicity caused by Cr(VI) in vivo. We reached the conclusion that Drp1-dependent mitochondrial fission contributes to Cr(VI)-induced mitophagy and hepatotoxicity, which may provide experimental basis for the study of chromium-associated toxicity, especially for the prevention of health damage in chromium-exposed population.
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影响因子：
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作者：
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影响因子：
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通讯作者：
Blackstone, Craig
DOI：
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发表时间：
2013
期刊：
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Hiromichi Hara;J. Araya;Saburo Ito;Kenji Kobayashi;Yutaka Yoshii;H. Wakui;Jun Kojima;Kenichiro Shimizu;T. Numata;M. Kawaishi;N. Kamiya;M. Odaka;T. Morikawa;Yumi;K. Nakayama;K. Kuwano
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影响因子：
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作者：
Germain, M;Mathai, JP;Shore, GC
通讯作者：
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