A dual mechanism of cytoprotection afforded by M-LDH in embryonic heart H9C2 cells

Sofija Jovanovic, Qingyou Du, Andriy Sukhodub, Aleksandar Jovanovic (Lead / Corresponding author)

    Research output: Contribution to journalArticlepeer-review

    24 Citations (Scopus)

    Abstract

    Muscle form of lactate dehydrogenase (M-LDH), a minor LDH form in cardiomyocytes, physically interacts with ATP-sensitive K+ (K-ATP) channel-forming subunits. Here, we have shown that expression of 193gly-M-LDH, an inactive mutant of M-LDH, inhibit regulation of the K-ATP channels activity by LDH substrates in embryonic rat heart H9C2 cells. In cells expressing 193gly-M-LDH chemical hypoxia has failed to activate K-ATP channels. The similar results were obtained in H9C2 cells expressing Kir6.2AFA, a mutant form of Kir6.2 with largely decreased K+ conductance. Kir6.2AFA has slightly, but significantly, reduced cellular survival under chemical hypoxia while the deleterious effect of 193gly-M-LDH was significantly more pronounced. The levels of total and subsarcolemmal ATP in H9C2 cells were not affected by Kir6.2AFA, but the expression of 193gly-M-LDH led to lower levels of subsarcolemmal ATP during chemical hypoxia. We conclude that M-LDH regulates both the channel activity and the levels of subsarcolemmal ATP and that both mechanism contribute to the M-LDH-mediated cytoprotection. (C) 2009 Elsevier B.V. All rights reserved.

    Original languageEnglish
    Pages (from-to)1379-1386
    Number of pages8
    JournalBiochimica et Biophysica Acta (BBA) - Molecular Cell Research
    Volume1793
    Issue number8
    DOIs
    Publication statusPublished - Aug 2009

    Keywords

    • Lactate dehydrogenase
    • K-ATP channel
    • H9C2 cell
    • Hypoxia
    • K-ATP CHANNELS
    • SENSITIVE POTASSIUM CHANNELS
    • PREVENTS MEMBRANE DEPOLARIZATION
    • CHEMICAL HYPOXIA-REOXYGENATION
    • RABBIT VENTRICULAR MYOCYTES
    • METABOLIC STRESS
    • GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE
    • SKELETAL-MUSCLE
    • RAT-HEART
    • CARDIOMYOCYTES

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