Nicotinamide-rich diet improves physical endurance by up-regulating SUR2A in the heart

Andriy Sukhodub, Rajni Sudhir, Qingyou Du, Sofija Jovanovic, Santiago Reyes, Aleksandar Jovanovic

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    Abstract

    SUR2A is an ATP-binding protein that serves as a regulatory subunit of cardioprotective ATP-sensitive K+ (KATP) channels. Based on signalling pathway regulating SUR2A expression and SUR2A role in regulating numbers of fully assembled KATP channels, we have suggested that nicotinamide-rich diet could improve physical endurance by stimulating SUR2A expression. We have found that mice on nicotinamide-rich diet significantly improved physical endurance, which was associated with significant increase in expression of SUR2A. Transgenic mice with solely overexpressed SUR2A on control diet had increased physical endurance in a similar manner as the wild-type mice on nicotinamide-rich diet. The experiments focused on action membrane potential and intracellular Ca2+ concentration have demonstrated that increased SUR2A expression was associated with the activation of sarcolemmal KATP channels and steady Ca2+ levels in cardiomyocytes in response to beta-adrenergic stimulation. In contrast, the same challenge in the wild-type was characterized by a lack of the channel activation and rise in intracellular Ca2+. Nicotinamide-rich diet was ineffective to increase physical endurance in mice lacking KATP channels. This study has shown that nicotinamide-rich diet improves physical endurance by increasing expression of SUR2A and that this is a sole mechanism of the nicotinamide-rich diet effect. The obtained results suggest that oral nicotinamide is a regulator of SUR2A expression and has a potential as a drug that can improve physical endurance in conditions where this effect would be desirable.

    Original languageEnglish
    Pages (from-to)1703-1712
    Number of pages10
    JournalJournal of Cellular and Molecular Medicine
    Volume15
    Issue number8
    DOIs
    Publication statusPublished - Aug 2011

    Keywords

    • nicotinamide
    • SUR2A
    • endurance
    • KATP channels
    • SENSITIVE K+ CHANNELS
    • ATP CHANNELS
    • H9C2 CELLS
    • ISCHEMIA
    • EXERCISE
    • KINASE
    • CARDIOMYOCYTES
    • MYOCARDIUM
    • EXPRESSION
    • MECHANISM

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