Cytoprotection by the NO-donor SNAP against ischemia/reoxygenation injury in mouse embryonic stem cell-derived cardiomyocytes

A. Görbe, Z. V. Varga, J. Pálóczi, S. Rungarunlert, N. Klincumhom, M. Pirity, R. Madonna, T. Eschenhagen, A. Dinnyés, T. Csont, P. Ferdinándy

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Embryonic 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.

Original languageEnglish
Pages (from-to)258-264
Number of pages7
JournalMolecular Biotechnology
Volume56
Issue number3
DOIs
Publication statusPublished - Mar 2014

Fingerprint

Penicillamine
Cytoprotection
Stem cells
Cardiac Myocytes
Ischemia
Cyclic GMP-Dependent Protein Kinases
Cell death
Proteins
Brain
Screening
Wounds and Injuries
KATP Channels
Guanylate Cyclase
Brain Natriuretic Peptide
Arginine
Molecules
Adenosinetriphosphate
Cell Death
Cells
Propidium

Keywords

  • Cardioprotection
  • Ischemia/reoxygenation
  • Nitric oxide
  • Signal-transduction
  • Stem cell

ASJC Scopus subject areas

  • Biochemistry
  • Biotechnology
  • Molecular Biology
  • Bioengineering
  • Applied Microbiology and Biotechnology

Cite this

Cytoprotection by the NO-donor SNAP against ischemia/reoxygenation injury in mouse embryonic stem cell-derived cardiomyocytes. / Görbe, A.; Varga, Z. V.; Pálóczi, J.; Rungarunlert, S.; Klincumhom, N.; Pirity, M.; Madonna, R.; Eschenhagen, T.; Dinnyés, A.; Csont, T.; Ferdinándy, P.

In: Molecular Biotechnology, Vol. 56, No. 3, 03.2014, p. 258-264.

Research output: Contribution to journalArticle

Görbe, A. ; Varga, Z. V. ; Pálóczi, J. ; Rungarunlert, S. ; Klincumhom, N. ; Pirity, M. ; Madonna, R. ; Eschenhagen, T. ; Dinnyés, A. ; Csont, T. ; Ferdinándy, P. / Cytoprotection by the NO-donor SNAP against ischemia/reoxygenation injury in mouse embryonic stem cell-derived cardiomyocytes. In: Molecular Biotechnology. 2014 ; Vol. 56, No. 3. pp. 258-264.
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AU - Varga, Z. V.

AU - Pálóczi, J.

AU - Rungarunlert, S.

AU - Klincumhom, N.

AU - Pirity, M.

AU - Madonna, R.

AU - Eschenhagen, T.

AU - Dinnyés, A.

AU - Csont, T.

AU - Ferdinándy, P.

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KW - Signal-transduction

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