铜通过AMPK-mTOR通路诱导猪下丘脑线粒体介导的细胞凋亡

Copper induces mitochondria-mediated apoptosis via AMPK-mTOR pathway in hypothalamus of Pigs

Keywords：Copper;Mitochondrion;Apoptosis;AMPK-mTOR pathway;Hypothalamus

关键词：铜;线粒体;细胞凋亡;AMPK-mTOR通路;下丘脑

哺乳动物：猪

作者：ChaiqinLei1JianzhaoLiao1QuanweiLiJianShiHuiZhangJianyingGuoQingyueHanLianmeiHuYingLiJiaqiangPanZhaoxinTang

出版期刊：《ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY》 2021/9/1

Abstract：

Copper (Cu), one of the heavy metals, is far beyond the carrying capacity of the environment with Cu mining, industrial wastewater discharging and the use of Cu-containing pesticides. Intaking excess Cu can cause toxic effects on liver, kidney, heart, but few studies report Cu toxicity on brain tissue. It is noteworthy that most toxicity tests are based on rodent models, but large mammals chosen as animal models has no reported. To explore the relationship of the Cu toxicity and mitochondria-mediated apoptosis on hypothalamus in pigs, the content of Cu, histomorphology, mitochondrial related indicators, apoptosis, and AMPK-mTOR signaling pathway were detected. Results showed that Cu could accumulate in hypothalamus and lead to mitochondrial dysfunction, evidenced by the decrease of ATP production, activities of respiratory chain complex I-IV, and mitochondrial respiratory function in Cu-treated groups. Additionally, the genes and proteins expression of Bax, Caspase-3, Cytc in treatment group were higher than control group. Furthermore, the protein level of p-AMPK was enhanced significantly and p-mTOR was declined, which manifested that AMPK-mTOR signaling pathway was activated in Cu-treated groups. In conclusion, this study illuminated that the accumulation of Cu could cause mitochondrial dysfunction, induce mitochondria-mediated apoptosis and activate AMPK-mTOR pathway in hypothalamus.

文章摘要：

铜（Cu）是重金属之一，随着铜矿开采、工业废水排放和含铜农药的使用，已远远超出环境的承载能力。摄入过量的铜会对肝脏、肾脏、心脏产生毒性作用，但很少有研究报告铜对脑组织的毒性。值得注意的是，大多数毒性试验都是基于啮齿动物模型，而选择大型哺乳动物作为动物模型的尚未见报道。为探讨Cu毒性与线粒体介导的猪下丘脑细胞凋亡的关系，检测了Cu含量、组织形态学、线粒体相关指标、细胞凋亡和AMPK-mTOR信号通路。结果表明，Cu 可以在下丘脑中积累并导致线粒体功能障碍，这可以通过 Cu 处理组中 ATP 产生、呼吸链复合物 I-IV 活性和线粒体呼吸功能的减少来证明。此外，治疗组Bax、Caspase-3、Cytc基因和蛋白表达均高于对照组。此外，p-AMPK蛋白水平显着增强，p-mTOR下降，表明铜处理组AMPK-mTOR信号通路被激活。总之，本研究表明，Cu 的积累可导致线粒体功能障碍，诱导线粒体介导的细胞凋亡并激活下丘脑中的 AMPK-mTOR 通路。

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