Methamphetamine induces cardiomyopathy by Sigmar1 inhibition-dependent impairment of mitochondrial dynamics and function.
Methamphetamine induces cardiomyopathy by Sigmar1 inhibition-dependent impairment of mitochondrial dynamics and function.
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DOI：
10.1038/s42003-020-01408-z
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发表时间：
2020-11-17
影响因子：
5.9
通讯作者：
Bhuiyan MS
中科院分区：
文献类型：
--
作者：
Abdullah CS;Aishwarya R;Alam S;Morshed M;Remex NS;Nitu S;Kolluru GK;Traylor J;Miriyala S;Panchatcharam M;Hartman B;King J;Bhuiyan MAN;Chandran S;Woolard MD;Yu X;Goeders NE;Dominic P;Arnold CL;Stokes K;Kevil CG;Orr AW;Bhuiyan MS
甲基苯丙胺相关性心肌病是与非法药物使用有关的死亡的主要原因。在这里，我们表明，Sigmar1是甲基苯丙胺相关性心肌病的治疗靶点，并使用人类心脏尸检样本和“狂欢和崩溃”甲基苯丙胺给药的小鼠模型定义了分子机制。Sigmar1的表达在人类甲基苯丙胺使用者的心脏和那些“狂欢和崩溃”甲基苯丙胺治疗的小鼠的心脏中显著降低。甲基苯丙胺使用者的心脏也显示出心肌病的迹象，包括细胞损伤，纤维化和心脏扩大。此外，暴露于“暴饮暴食”甲基苯丙胺的小鼠发生心脏肥大、纤维化重塑和线粒体功能障碍，导致收缩功能障碍。甲基苯丙胺治疗抑制Sigmar1，导致cAMP反应元件结合蛋白（CREB）失活，线粒体裂变1蛋白（FIS 1）表达减少，并最终改变线粒体动力学和功能。因此，Sigmar1是一种可行的治疗药物，用于预防甲基苯丙胺相关性心肌病。Chowdhury Abdulla和Richa Aishwarya等人报道，小鼠接触甲基苯丙胺通过信号受体Sigmar1导致心肌病。他们发现甲基苯丙胺抑制Sigmar1，从而改变线粒体功能，并表明他们的发现与人类甲基苯丙胺使用者心脏的观察结果一致。
Methamphetamine-associated cardiomyopathy is the leading cause of death linked with illicit drug use. Here we show that Sigmar1 is a therapeutic target for methamphetamine-associated cardiomyopathy and defined the molecular mechanisms using autopsy samples of human hearts, and a mouse model of “binge and crash” methamphetamine administration. Sigmar1 expression is significantly decreased in the hearts of human methamphetamine users and those of “binge and crash” methamphetamine-treated mice. The hearts of methamphetamine users also show signs of cardiomyopathy, including cellular injury, fibrosis, and enlargement of the heart. In addition, mice expose to “binge and crash” methamphetamine develop cardiac hypertrophy, fibrotic remodeling, and mitochondrial dysfunction leading to contractile dysfunction. Methamphetamine treatment inhibits Sigmar1, resulting in inactivation of the cAMP response element-binding protein (CREB), decreased expression of mitochondrial fission 1 protein (FIS1), and ultimately alteration of mitochondrial dynamics and function. Therefore, Sigmar1 is a viable therapeutic agent for protection against methamphetamine-associated cardiomyopathy. Chowdhury Abdulla and Richa Aishwarya et al. report that methamphetamine exposure in mice leads to cardiomyopathy via the signaling receptor Sigmar1. They find that methamphetamine inhibits Sigmar1, which alters mitochondrial function, and show that their findings are consistent with observations in hearts from human methamphetamine users.
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影响因子：
15.9
作者：
Fentzke, RC;Korcarz, CE;Leiden, JM
通讯作者：
Leiden, JM
影响因子：
8
作者：
Eraso-Pichot, A.;Larramona-Arcas, R.;Masgrau, R.
通讯作者：
Masgrau, R.
DOI：
10.1124/jpet.113.208264
发表时间：
2014-01-01
影响因子：
3.5
作者：
Hiranita, Takato;Kohut, Stephen J.;Katz, Jonathan L.
通讯作者：
Katz, Jonathan L.
影响因子：
7.7
作者：
Costes S;Vandewalle B;Tourrel-Cuzin C;Broca C;Linck N;Bertrand G;Kerr-Conte J;Portha B;Pattou F;Bockaert J;Dalle S
通讯作者：
Dalle S
影响因子：
5.4
作者：
Alam S;Abdullah CS;Aishwarya R;Miriyala S;Panchatcharam M;Peretik JM;Orr AW;James J;Robbins J;Bhuiyan MS
通讯作者：
Bhuiyan MS