title: The role of the inhibition of glutathione-S-transferase in the protective mechanisms of ischemic postconditioning.
abstract: 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.
authors.affiliation: Department of Surgical Research and Techniques, Medical Faculty, University of Pécs, Kodály Zoltán St. 20, H-7624 Pécs, Hungary. balatonyibori@gmail.com
authors.forename: Borbála
authors.initials: B
authors.lastname: Balatonyi
authors.forename: Balázs
authors.initials: B
authors.lastname: Gasz
authors.forename: Viktória
authors.initials: V
authors.lastname: Kovács
authors.forename: János
authors.initials: J
authors.lastname: Lantos
authors.forename: Gábor
authors.initials: G
authors.lastname: Jancsó
authors.forename: Nándor
authors.initials: N
authors.lastname: Marczin
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Rőth
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004976:Ethacrynic Acid / Q000494:pharmacology; D005434:Flow Cytometry; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors* / Q000502:physiology*; D057775:Ischemic Postconditioning; D008954:Models, Biological; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000473:pathology / Q000517:prevention & control*; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D010865:Pilot Projects; D051381:Rats; D017208:Rats, Wistar
chemical_list: D004791:Enzyme Inhibitors; D005982:Glutathione Transferase; D004976:Ethacrynic Acid