The role of the inhibition of glutathione-S-transferase in the protective mechanisms of ischemic postconditioning

Balatonyi, Borbála and Gasz, Balázs and Kovács, Viktória and Lantos, János and Jancsó, Gábor and Marczin, Nándor and Rőth, Erzsébet (2013) The role of the inhibition of glutathione-S-transferase in the protective mechanisms of ischemic postconditioning. CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY, 91 (8). pp. 625-632. ISSN 0008-4212

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The antioxidant glutathione-S-transferase (GST) is a crucial determinant of the development of ischaemic-reperfusion (I/R) injury, and plays a pivotal role in the regulation of the mitogen activated protein kinase (MAPK) pathways involved in stress response and apoptosis. The aim of this study was to investigate whether inhibition of GST can abolish the benefit of ischaemic postconditioning (IPoC). A neonatal rat cardiomyocyte cell culture was prepared and divided into 6 groups: (I) control group without treatment; (II) cells exposed to simulated I/R; (III) simulated I/R (sI/R) with IPoC; (IV) ethacrynic acid (EA) alone; (V) sI/R with EA; and (VI) sI/R and IPoC together with EA. Viability of the cells was measured by MTT assay, the quantity of apoptotic cells was assessed by flow cytometry following annexin V-FITC - propidium-iodide double staining. The activation of JNK, p38, ERK/p42-p44 MAPKs, and GSK-3β protein kinase was determined by flow-cytometric assay. GST inhibition markedly increased the apoptosis and decreased the cell viability despite IPoC. The protective effect of IPoC was lost in GST-inhibited groups for all MAPKs and GSK-3β. GST activity is required for the survival of cultured cardiomyocytes under stress conditions. GST inhibition was associated with differential activation of MAP and the protein kinases regulating these pathways in the process of ischaemic postconditioning.

Item Type: Article
Uncontrolled Keywords: primer cardiomyocyte cell culture, ischaemic postconditioning(IPoC); glutatione-S-transferase(GST); ethacryn acid (EA); cell viability; apoptosis; mitogen activated protein kinase (MAPK)
Subjects: R Medicine / orvostudomány > RZ Other systems of medicine / orvostudomány egyéb területei
Depositing User: xGabriella xBeke
Date Deposited: 11 Jul 2014 09:01
Last Modified: 11 Jul 2014 09:01

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