Sigma-1 receptor is involved in modification of ER-mitochondria proximity and Ca2+ homeostasis in cardiomyocytes

Hideaki Tagashira; Md Shenuarin Bhuiyan; Yasuharu Shinoda; Ichiro Kawahata; Tomohiro Numata; Kohji Fukunaga

doi:10.1016/j.jphs.2022.12.005

Sigma-1 receptor is involved in modification of ER-mitochondria proximity and Ca²⁺ homeostasis in cardiomyocytes

J Pharmacol Sci. 2023 Feb;151(2):128-133. doi: 10.1016/j.jphs.2022.12.005. Epub 2022 Dec 19.

Authors

Hideaki Tagashira¹, Md Shenuarin Bhuiyan², Yasuharu Shinoda³, Ichiro Kawahata³, Tomohiro Numata⁴, Kohji Fukunaga⁵

Affiliations

¹ Department of Integrative Physiology, Graduate School of Medicine, Akita University, Akita, Japan; Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. Electronic address: htagashia@med.akita-u.ac.jp.
² Department of Pathology and Translational Pathobiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA; Department of Molecular and Cellular Physiology, Louisiana State University Health Sciences Center-Shreveport, Shreveport, LA, USA.
³ Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.
⁴ Department of Integrative Physiology, Graduate School of Medicine, Akita University, Akita, Japan.
⁵ Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan. Electronic address: kfukunaga@tohoku.ac.jp.

PMID: 36707178
DOI: 10.1016/j.jphs.2022.12.005

Abstract

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.

Keywords: Cardiac hypertrophy; Mitochondria; Sigma receptors.

MeSH terms

Animals
Calcium / metabolism
Endoplasmic Reticulum / metabolism
Heart Failure*
Homeostasis / genetics
Mice
Mitochondria
Myocytes, Cardiac / metabolism
Rats
Receptors, sigma* / genetics
Receptors, sigma* / metabolism
Sigma-1 Receptor

Substances

Receptors, sigma
Calcium