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Inhibition of reverse-mode sodium-calcium exchanger activity and apoptosis by levosimendan in human cardiomyocyte progenitor cell-derived cardiomyocytes after anoxia and reoxygenation.
- Source :
-
PloS one [PLoS One] 2014 Feb 03; Vol. 9 (2), pp. e85909. Date of Electronic Publication: 2014 Feb 03 (Print Publication: 2014). - Publication Year :
- 2014
-
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.
- Subjects :
- Adolescent
Blotting, Western
Cardiotonic Agents pharmacology
Cell Hypoxia
Cell Membrane drug effects
Cell Membrane metabolism
Cells, Cultured
Child
Endoplasmic Reticulum Stress drug effects
Female
Flow Cytometry
HEK293 Cells
Humans
Male
Microscopy, Confocal
Myocytes, Cardiac cytology
Myocytes, Cardiac metabolism
Oxygen pharmacology
RNA Interference
Simendan
Sodium-Calcium Exchanger genetics
Sodium-Calcium Exchanger metabolism
Stem Cells metabolism
Apoptosis drug effects
Hydrazones pharmacology
Myocytes, Cardiac drug effects
Pyridazines pharmacology
Sodium-Calcium Exchanger antagonists & inhibitors
Stem Cells drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 9
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 24498266
- Full Text :
- https://doi.org/10.1371/journal.pone.0085909