Exogenous Nitric Oxide Protects Human Embryonic Stem Cell-Derived Cardiomyocytes against Ischemia/Reperfusion Injury

János Pálóczi, Zoltán V. Varga, Ágota Apáti, Kornélia Szebényi, Balázs Sarkadi, Rosalinda Madonna, Raffaele De Caterina, Tamás Csont, Thomas Eschenhagen, Péter Ferdinandy, Anikó Görbe

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background and Aims. Human embryonic stem cell- (hESC-) derived cardiomyocytes are one of the useful screening platforms of potential cardiocytoprotective molecules. However, little is known about the behavior of these cardiomyocytes in simulated ischemia/reperfusion conditions. In this study, we have tested the cytoprotective effect of an NO donor and the brain type natriuretic peptide (BNP) in a screening platform based first on differentiated embryonic bodies (EBs, 6 + 4 days) and then on more differentiated cardiomyocytes (6 + 24 days), both derived from hESCs. Methods. Both types of hESC-derived cells were exposed to 150 min simulated ischemia, followed by 120 min reperfusion. Cell viability was assessed by propidium iodide staining. The following treatments were applied during simulated ischemia in differentiated EBs: the NO-donor S-nitroso-N-acetylpenicillamine (SNAP) (10-7, 10-6, and 10-5 M), BNP (10-9, 10-8, and 10-7 M), and the nonspecific NO synthase inhibitor Nω-nitro-L-arginine (L-NNA, 10-5 M). Results. SNAP (10-6, 10-5 M) significantly attenuated cell death in differentiated EBs. However, simulated ischemia/reperfusion-induced cell death was not affected by BNP or by L-NNA. In separate experiments, SNAP (10-6 M) also protected hESC-derived cardiomyocytes. Conclusions. We conclude that SNAP, but not BNP, protects differentiated EBs or cardiomyocytes derived from hESCs against simulated ischemia/reperfusion injury. The present screening platform is a useful tool for discovery of cardiocytoprotective molecules and their cellular mechanisms.

Original languageEnglish
Article number4298945
JournalOxidative medicine and cellular longevity
Volume2016
DOIs
Publication statusPublished - Jan 1 2016

ASJC Scopus subject areas

  • Biochemistry
  • Ageing
  • Cell Biology

Fingerprint Dive into the research topics of 'Exogenous Nitric Oxide Protects Human Embryonic Stem Cell-Derived Cardiomyocytes against Ischemia/Reperfusion Injury'. Together they form a unique fingerprint.

  • Cite this