A. GörbeZ. V. VargaJ. PálócziS. RungarunlertN. KlincumhomM. K. PirityR. MadonnaT. EschenhagenA. DinnyésT. CsontP. FerdinandyCardiovascular Research Group, SzegedChulalongkorn UniversitySzent Istvan EgyetemUniversitatsklinikum Hamburg-Eppendorf und Medizinische FakultatBioTalentum Ltd.Texas Heart InstituteSemmelweis EgyetemPharmahungary GroupBiological Research Center at Hungarian Academy of SciencesUniversity of G. d'Annunzio Chieti and PescaraMahidol University2018-11-092018-11-092014-03-01Molecular Biotechnology. Vol.56, No.3 (2014), 258-26415590305107360852-s2.0-84896715484https://repository.li.mahidol.ac.th/handle/123456789/33299Embryonic stem cell (ESC)-derived cardiomyocytes are a promising cell source for the screening for potential cytoprotective molecules against ischemia/reperfusion injury, however, little is known on their behavior in hypoxia/reoxygenation conditions. Here we tested the cytoprotective effect of the NO-donor SNAP and its downstream cellular pathway. Mouse ESC-derived cardiomyocytes were subjected to 150-min simulated ischemia (SI) followed by 120-min reoxygenation or corresponding non-ischemic conditions. The following treatments were applied during SI or normoxia: the NO-donor S-Nitroso-N-acetyl- d,l-penicillamine (SNAP), the protein kinase G (PKG) inhibitor, the K ATP channel blocker glibenclamide, the particulate guanylate cyclase activator brain type natriuretic peptide (BNP), and a non-specific NO synthase inhibitor (N-Nitro-l-arginine, l-NNA) alone or in different combinations. Viability of cells was assayed by propidium iodide staining. SNAP attenuated SI-induced cell death in a concentration-dependent manner, and this protection was attenuated by inhibition of either PKG or KATP channels. However, SI-induced cell death was not affected by BNP or by l-NNA. We conclude that SNAP protects mESC-derived cardiomyocytes against SI/R injury and that soluble guanylate-cyclase, PKG, and KATP channels play a role in the downstream pathway of SNAP-induced cytoprotection. The present mESC-derived cardiomyocyte-based screening platform is a useful tool for discovery of cytoprotective molecules. © 2013 Springer Science+Business Media New York.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyChemical EngineeringImmunology and MicrobiologyArticleSCOPUS10.1007/s12033-013-9704-2