Glutathione-related substances maintain cardiomyocyte contractile function in hypoxic conditions
| Autor: | Mikhail S. Novikov, A A Abramov, Alexander A. Makarov, Vladimir A. Mitkevich, Irina Yu. Petrushanko, Valentina A. Lakunina, Yuri M. Poluektov, Asker Y. Khapchaev, Vladimir P. Shirinsky, Valery I. Kapelko, Vladimir L. Lakomkin, Nidas A. Undrovinas |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Protein subunit lcsh:Medicine Article Contractility 03 medical and health sciences chemistry.chemical_compound Organ Culture Techniques 0302 clinical medicine medicine Animals Humans Myocyte Myocytes Cardiac Calcium Signaling Sulfhydryl Compounds lcsh:Science Multidisciplinary Sarcolemma Glutathione Disulfide lcsh:R Cardiac myocyte Arrhythmias Cardiac Heart Transporter Glutathione Hypoxia (medical) Myocardial Contraction Cell Hypoxia Electric Stimulation Rats Cell biology Oxygen 030104 developmental biology chemistry S-Nitrosoglutathione lcsh:Q medicine.symptom 030217 neurology & neurosurgery Muscle Contraction |
| Zdroj: | Scientific Reports Scientific Reports, Vol 9, Iss 1, Pp 1-12 (2019) |
| ISSN: | 2045-2322 |
| Popis: | Severe hypoxia leads to decline in cardiac contractility and induces arrhythmic events in part due to oxidative damage to cardiomyocyte proteins including ion transporters. This results in compromised handling of Ca2+ ions that trigger heart contractile machinery. Here, we demonstrate that thiol-containing compounds such as N-acetylcysteine (NAC), glutathione ethyl ester (et-GSH), oxidized tetraethylglutathione (tet-GSSG), oxidized glutathione (GSSG) and S-nitrosoglutathione (GSNO) are capable of reducing negative effects of hypoxia on isolated rat cardiomyocytes. Preincubation of cardiomyocytes with 0.1 mM GSNO, 0.5 mM et-GSH, GSSG, tet-GSSG or with 10 mM NAC allows cells 5-times longer tolerate the hypoxic conditions and elicit regular Ca2+ transients in response to electric pacing. The shape of Ca2+ transients generated in the presence of GSNO, et-GSH and NAC was similar to that observed in normoxic control cardiomyocytes. The leader compound, GSNO, accelerated by 34% the recovery of normal contractile function of isolated rat heart subjected to ischemia-reperfusion. GSNO increased glutathionylation of Na,K-ATPase alpha-2 subunit, the principal ion-transporter of cardiac myocyte sarcolemma, which prevents irreversible oxidation of Na,K-ATPase and regulates its function to support normal Ca2+ ion handling in hypoxic cardiomyocytes. Altogether, GSNO appears effective cardioprotector in hypoxic conditions worth further studies toward its cardiovascular application. |
| Databáze: | OpenAIRE |
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