M-LDH physically associated with sarcolemmal K-ATP channels mediates cytoprotection in heart embryonic H9C2 cells

Sofija Jovanovic, Qingyou Du, Andriy Sukhodub, Aleksandar Jovanovic

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    Abstract

    Muscle form of lactate dehydrogenase (M-LDH) physically associate with K-ATP, channel subunits, Kir6.2 and SUR2A, and is an integral part of the ATP-sensitive K+ (K-ATP) channel protein complex in the heart. Here, we have shown that concomitant introduction of viral constructs containing truncated and mutated forms of M-LDH (Delta M-LDH) and 193gly-M-LDH respectively, generate a phenotype of rat heart embryonic H9C2 cells that do not contain functional M-LDH as a part of the K-ATP, channel protein complex. The K+ current was increased in wild type cells, but not in cells expressing Delta M-LDH/193gly-M-LDH. when they were exposed to chemical hypoxia induced by 2,4 dinitrophenol (DNP: 10 mM). At the same time, the outcome of chemical hypoxia was much worse in Delta M-LDH/193gly-M-LDH phenotype than in the control one, and that was associated with increased loss of intracellular ATP in cells infected with Delta M-LDH/193gly-M-LDH. On the other hand, cells expressing Kir6.2AFA. a Kir6.2 mutant that abolishes K-ATP channel conductance without affecting intracellular ATP levels. survived chemical hypoxia much better than cells expressing Delta M-LDH/193gly-M-LDH. Based on the obtained results. we conclude that M-LDH physically associated with Kir6.2/SUR2A regulates the activity of sarcolemmal K-ATP channels as well as an intracellular ATP production during metabolic stress, both of which are important for cell survival. (C) 2009 Elsevier Ltd. All rights reserved.

    Original languageEnglish
    Pages (from-to)2295-2301
    Number of pages7
    JournalInternational Journal of Biochemistry & Cell Biology
    Volume41
    Issue number11
    DOIs
    Publication statusPublished - Nov 2009

    Keywords

    • M-LDH
    • K-ATP channels
    • Chemical hypoxia
    • ATP
    • H9C2 cells
    • PREVENTS MEMBRANE DEPOLARIZATION
    • CHEMICAL HYPOXIA-REOXYGENATION
    • SENSITIVE POTASSIUM CHANNELS
    • GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE
    • CARDIOMYOCYTES
    • KINASE
    • EXPRESSION
    • ISCHEMIA
    • SUBUNITS
    • SERVES

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