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PLoS One. 2014 Feb 3;9(2):e85909. doi: 10.1371/journal.pone.0085909. eCollection 2014.

Inhibition of reverse-mode sodium-calcium exchanger activity and apoptosis by levosimendan in human cardiomyocyte progenitor cell-derived cardiomyocytes after anoxia and reoxygenation.

Author information

1
Department of Surgery, Division of Cardiovascular Surgery, China Medical University Hospital, Taichung, Taiwan ; Department of Life Science, Tunghai University, Taichung, Taiwan.
2
Department of Life sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan.
3
Department of Life Science, Tunghai University, Taichung, Taiwan.
4
Clinical Immunology Center, China Medical University Hospital, Taichung, Taiwan ; College of Medicine, China Medical University, Taichung, Taiwan.

Abstract

Levosimendan, a known calcium sensitizer with positive inotropic and vasodilating properties, might also be cardioprotective during ischemia-reperfusion (I/R) insult. Its effects on calcium homeostasis and apoptosis in I/R injury remain unclear. Na(+)/Ca(2+) exchanger (NCX) is a critical mediator of calcium homeostasis in cardiomyocytes, with reverse-mode NCX activity responsible for intracellular calcium overload and apoptosis of cardiomyocytes during I/R. We probed effects and underlying mechanisms of levosimendan on apoptosis and NCX activity in cultured human cardiomyocyte progenitor cells (CPC)-derived cardiomyocytes undergoing anoxia-reoxygenation (A/R), simulating I/R in vivo. Administration of levosimendan decreased apoptosis of CPC-derived cardiomyocytes induced by A/R. The increase in reverse-mode NCX activity after A/R was curtailed by levosimendan, and NCX1 was translocated away from the cell membrane. Concomitantly, endoplasmic reticulum (ER) stress response induced by A/R was attenuated in CPC-derived cardiomycytes treated with NCX-targeted siRNA or levosimendan, with no synergistic effect between treatments. Results indicated levosimendan inhibited reverse-mode NCX activity to protect CPC-derived cardiomyocytes from A/R-induced ER stress and cell death.

PMID:
24498266
PMCID:
PMC3911900
DOI:
10.1371/journal.pone.0085909
[Indexed for MEDLINE]
Free PMC Article

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