Homocysteine induces mitochondrial dysfunction involving the crosstalk between oxidative stress and mitochondrial pSTAT3 in rat ischemic brain.
Homocysteine induces mitochondrial dysfunction involving the crosstalk between oxidative stress and mitochondrial pSTAT3 in rat ischemic brain.
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同型半胱氨酸诱导大鼠缺血脑线粒体功能障碍，涉及氧化应激和线粒体 pSTAT3 之间的串扰
DOI：
10.1038/s41598-017-07112-z
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发表时间：
2017-07-31
影响因子：
4.6
通讯作者：
Zhang X
中科院分区：
文献类型：
--
作者：
Chen S;Dong Z;Zhao Y;Sai N;Wang X;Liu H;Huang G;Zhang X
同型半胱氨酸 (Hcy) 已被证明对缺血性脑细胞具有神经毒性作用；然而，其根本机制仍不完全清楚。在这里，我们检查了 Hcy 治疗是否影响大鼠缺血脑中的线粒体损伤、氧化应激和线粒体 STAT3 (mitoStat3) 表达。我们的结果表明，Hcy治疗加重了局灶性脑缺血后大脑皮层和海马齿状回区域线粒体超微结构的损伤。除了细胞色素 c 释放增加之外，Hcy 水平升高还伴随着线粒体复合物 I-III 酶活性的显着抑制。 Hcy 处理的动物中 8-羟基-2'-脱氧鸟苷 (8-OHdG) 含量和 mitoStat3 蛋白磷酸化水平增加，而 Jak2 抑制剂 AG490 抑制 Hcy 诱导的 mitoStat3 磷酸化以及 8-OHdG 水平。 体外研究表明，Hcy 还显着增加活性氧 (ROS) 和 mitoStat3 水平。此外，抑制pSTAT3可减少Hcy介导的ROS水平增加，而使用ROS抑制剂谷胱甘肽乙酯淬灭ROS可抑制Neuro2a细胞中Hcy介导的pSTAT3过度激活。这些发现表明，开发干扰ROS/pSTAT3通路的疗法可能有助于治疗与Hcy相关的脑梗塞相关疾病。
Homocysteine (Hcy) has been shown to have a neurotoxic effect on ischemic brain cells; however, the underlying mechanisms remain incompletely understood. Here, we examined whether Hcy treatment influences mitochondria injury, oxidative stress, and mitochondrial STAT3 (mitoStat3) expression in rat ischemic brain. Our results demonstrated that Hcy treatment aggravated the damage of mitochondrial ultrastructure in the brain cortex and the dentate gyrus region of the hippocampus after focal cerebral ischemia. An elevated Hcy level was also accompanied by the significant inhibition of mitochondrial complex I–III enzymatic activities in addition to an increase in cytochrome c release. 8-Hydroxy-2′-deoxyguanosine (8-OHdG) content and mitoStat3 protein phosphorylation level were increased in Hcy-treated animals, whereas AG490, a Jak2 inhibitor, inhibited mitoStat3 phosphorylation as well as 8-OHdG levels induced by Hcy.In vitrostudies revealed that Hcy also markedly increased reactive oxygen species (ROS) and mitoStat3 levels. In addition, the inhibition of pSTAT3 reduced Hcy-mediated increase in ROS levels, whereas quenching ROS using the ROS inhibitor glutathione ethyl ester inhibited Hcy-mediated pSTAT3 overactivation in Neuro2a cells. These findings suggest that the development of therapies that interfere with the ROS/pSTAT3 pathway may be helpful for treating cerebral infarction-related diseases associated with Hcy.
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影响因子：
8.3
作者：
Baek SH;Noh AR;Kim KA;Akram M;Shin YJ;Kim ES;Yu SW;Majid A;Bae ON
通讯作者：
Bae ON
影响因子：
5.6
作者：
Li W;Jiang M;Zhao S;Liu H;Zhang X;Wilson JX;Huang G
通讯作者：
Huang G
在缺血性卒中大鼠模型中，来自脑提取的间充质干细胞的微泡改善了神经功能。
影响因子：
4.6
作者：
Lee JY;Kim E;Choi SM;Kim DW;Kim KP;Lee I;Kim HS
通讯作者：
Kim HS
影响因子：
5.3
作者：
Bukharaeva E;Shakirzyanova A;Khuzakhmetova V;Sitdikova G;Giniatullin R
通讯作者：
Giniatullin R
影响因子：
4.2
作者：
Bhattacharjee, Nivedita;Borah, Anupom
通讯作者：
Borah, Anupom