Excess sarcoplasmic reticulum-mitochondria calcium transport induced by Sphingosine-1-phosphate contributes to cardiomyocyte hypertrophy.

Autor: Qi Y; The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China., Li JJ; The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China., Di XH; The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China., Zhang Y; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China., Chen JL; The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China., Wu ZX; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China., Man ZY; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China., Bai RY; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China., Lu F; State Key Laboratory of Membrane Biology, Institute of Molecular Medicine, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China., Tong J; The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China., Liu XL; The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China., Deng XL; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China., Zhang J; The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China., Zhang X; Department of Aerospace Medicine, Fourth Military Medical University, Xi'an, Shaanxi 710032, China., Zhang Y; Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi 710061, China. Electronic address: zhangyixjtu@xjtu.edu.cn., Xie W; The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi 710049, China. Electronic address: xiewenjun@xjtu.edu.cn.
Jazyk: angličtina
Zdroj: Biochimica et biophysica acta. Molecular cell research [Biochim Biophys Acta Mol Cell Res] 2021 Apr; Vol. 1868 (5), pp. 118970. Date of Electronic Publication: 2021 Jan 30.
DOI: 10.1016/j.bbamcr.2021.118970
Abstrakt: Sphingosine-1-phosphate (S1P) has been shown to possess pro-hypertrophic properties in the heart, but the detailed molecular mechanism that underlies the pathological process is rarely explored. In the present study, we aim to explore the role of S1P-mediated intracellular Ca 2+ signaling, with a focus on sarcoplasmic reticulum (SR)-mitochondria communication, in cardiomyocyte hypertrophy. Cultured neonatal rat ventricular myocytes (NRVMs) displayed significantly hypertrophic growth after treatment with 1 μmol/L S1P for 48 h, as indicated by the cell surface area or mRNA expressions of hypertrophic marker genes (ANP, BNP and β-MHC). Importantly, mitochondrial Ca 2+ and reactive oxygen species (ROS) levels were dramatically elevated upon S1P stimulation, and pharmacological blockage of which abolished NRVM hypertrophy. 0.5 Hz electrical pacing induced similar cytosolic Ca 2+ kinetics to S1P stimulation, but unaffected the peak of mitochondrial [Ca 2+ ]. With interference of the expression of type 2 inositol 1,4,5-trisphosphate receptors (IP 3 R2), which are unemployed in electrical paced Ca 2+ activity but may be activated by S1P, alteration in mitochondrial Ca 2+ as well as the hypertrophic effect in NRVMs under S1P stimulation were attenuated. The hypertrophic effect of S1P can also be abolished by pharmacological block of S1PR1 or Gi signaling. Collectively, our study highlights the mechanistic role of IP 3 R2-mediated excess SR-mitochondria Ca 2+ transport in S1P-induced cardiomyocyte hypertrophy.
(Copyright © 2021 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE