Sigma-1 receptor is involved in modification of ER-mitochondria proximity and Ca2+ homeostasis in cardiomyocytes
Sigma-1 receptor is involved in modification of ER-mitochondria proximity and Ca2+ homeostasis in cardiomyocytes
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Sigma-1 受体参与心肌细胞内质网线粒体邻近性和 Ca2 稳态的修饰
DOI：
10.1016/j.jphs.2022.12.005
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发表时间：
2023
影响因子：
3.5
通讯作者：
Fukunaga Kohji
中科院分区：
文献类型：
--
作者：
Tagashira Hideaki;Bhuiyan Md. Shenuarin;Shinoda Yasuharu;Kawahata Ichiro;Numata Tomohiro;Fukunaga Kohji
Sigma-1受体（Sigmar 1）在具有线粒体功能障碍的心力衰竭模型小鼠中下调。然而，详细的机制还没有被调查。在这项研究中，我们研究了Sigmar 1在ER-线粒体接近Sigmar 1敲低或过表达的新生大鼠心室肌细胞（NRVMs）的作用。内皮素-1（ET-1）诱导的心肌细胞肥大在Sigmar 1敲低的NRVM中随着线粒体功能和ER-线粒体连接形成的失调而加重，而在Sigmar 1过表达的NRVM中则得到改善。我们的数据表明，心脏Sigmar 1的减少导致线粒体Ca 2+内流减少，促进线粒体分裂，随后减少ER-线粒体接近，加重ET-1诱导的心肌细胞损伤。
The Sigma-1 receptor (Sigmar1) is downregulated in heart failure model mice with mitochondrial dysfunction. However, the mechanism in detail has not been investigated. In this study, we investigated the role of Sigmar1 in ER-mitochondria proximity using Sigmar1-knockdown or -overexpressed neonatal rat ventricular myocytes (NRVMs). The endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy was aggravated with the dysregulation of mitochondrial function and ER-mitochondrial junctional formation in Sigmar1-knockdown NRVMs, whereas improved in Sigmar1 overexpressed NRVMs. Our data suggests that the reduction of the cardiac Sigmar1 results in decrease mitochondrial Ca2+influx and promotes mitochondrial fission, followed by reduced ER-mitochondria proximity, exacerbating ET-1-induced cardiomyocyte injury.