Copper-induced apoptosis and autophagy through oxidative stress-mediated mitochondrial dysfunction in male germ cells
Copper-induced apoptosis and autophagy through oxidative stress-mediated mitochondrial dysfunction in male germ cells
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DOI：
10.1016/j.tiv.2019.104639
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发表时间：
2019-12-01
影响因子：
3.2
通讯作者：
Li, Ying
中科院分区：
文献类型：
--
作者：
Kang, Zhenlong;Qiao, Na;Li, Ying
过量的铜会减少精子数量和活力，但原因尚不清楚。我们研究了铜暴露对永生化雄性生殖细胞系GC-1的毒性作用。铜除了改变细胞的活力和形态的剂量依赖性的方式。铜的添加导致活性氧（ROS），丙二醛（MDA）和乳酸脱氢酶（LDH）的水平增加，而过氧化氢酶（CAT）活性和谷胱甘肽（GSH）下降。线粒体跨膜电位和ATP水平下降，响应于铜的线粒体分裂，导致线粒体功能障碍。细胞凋亡率也与生长培养基中铜的水平成正比。铜还下调Bcl 2和上调Bax，Casp 8和Casp 3，将铜的作用与细胞凋亡增加联系起来。自噬相关基因（Atg 3、Atg 5、p62、Lc 3b/Lc 3a）和蛋白质（Lc 3b/Lc 3a、BECN 1、Atg 5、p62）的mRNA水平在铜处理的细胞中均增加，荧光显微镜测定的Lc 3水平也增加。这些结果表明，铜诱导细胞凋亡和自噬通过氧化应激介导的线粒体功能障碍。
Excess copper reduces sperm number and motility but the causes are unclear. We investigated the toxic effects of copper exposure on the immortalized male germ cell line GC-1. Copper addition to cells altered viability and morphology in a dose-dependent manner. Copper addition resulted in increased levels of reactive oxygen species (ROS), malonaldehyde (MDA) and lactate dehydrogenase (LDH) while catalase (CAT) activity and glutathione (GSH) declined. The mitochondrial transmembrane potential and ATP levels decreased in response to copper as did mitochondria fission that led to mitochondrial dysfunction. The apoptosis rate was also proportional to the level of copper in the growth medium. Copper also down-regulated Bcl2 and up-regulated Bax, Casp8 and Casp3 linking the effects of copper to increased apoptosis. The levels of mRNA for the autophagy-related genes (Atg3, Atg5, p62, Lc3b/Lc3a) and proteins (Lc3b/Lc3a, BECN1, Atg5, p62) all increased in copper-treated cells as were levels Lc3 determined by fluorescence microscopy. These results indicated that copper induces apoptosis and autophagy through oxidative stress-mediated mitochondrial dysfunction.