Salvage of nicotinamide adenine dinucleotide plays a critical role in the bioenergetic recovery of post-hypoxic cardiomyocytes

Domokos Gero, Csaba Szabo

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    Background and Purpose Ischaemic heart disease can lead to serious, life-threatening complications. Traditional therapies for ischaemia aim to increase oxygen delivery and reduce the myocardial ATP consumption by increasing the coronary perfusion and by suppressing cardiac contractility, heart rate or blood pressure. An adjunctive treatment option for ischaemia is to improve or optimize myocardial metabolism. Experimental Approach Metabolic suppression in the ischaemic heart is characterized by reduced levels of high-energy molecules: ATP and NAD+. Because NAD+ is required for most metabolic processes that generate ATP, we hypothesized that restoration of NAD+ would be a prerequisite for ATP regeneration and examined the role of the major NAD+ anabolic and catabolic pathways in the bioenergetic restoration process following oxygen-glucose deprivation injury in a cardiomyocyte cell line (H9c2 cells). Key Results Salvage of NAD+ via nicotinamide phosphoribosyl transferase was essential for bioenergetic recovery in cardiomyocytes. Blockade of nicotinamide phosphoribosyl transferase prevented the restoration of the cellular ATP pool following oxygen-glucose deprivation injury by inhibiting both the aerobic and anaerobic metabolism in the cardiomyocytes. NAD+ consumption by PARP-1 also undermined the recovery processes, and PARP inhibition significantly improved the metabolism and increased cellular ATP levels in cardiomyocytes. Conclusions and Implications We conclude that the NAD+ salvage pathway is essential for bioenergetic recovery in post-hypoxic cardiomyocytes and PARP inhibition may represent a potential future therapeutic intervention in ischaemic heart disease.

    Original languageEnglish (US)
    Pages (from-to)4817-4832
    Number of pages16
    JournalBritish Journal of Pharmacology
    Volume172
    Issue number20
    DOIs
    StatePublished - Oct 1 2015

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    Cardiac Myocytes
    NAD
    Energy Metabolism
    Adenosine Triphosphate
    Niacinamide
    Oxygen
    Transferases
    Myocardial Ischemia
    Ischemia
    Anaerobiosis
    Glucose
    Wounds and Injuries
    Regeneration
    Perfusion
    Heart Rate
    Blood Pressure
    Cell Line
    Therapeutics

    ASJC Scopus subject areas

    • Pharmacology

    Cite this

    Salvage of nicotinamide adenine dinucleotide plays a critical role in the bioenergetic recovery of post-hypoxic cardiomyocytes. / Gero, Domokos; Szabo, Csaba.

    In: British Journal of Pharmacology, Vol. 172, No. 20, 01.10.2015, p. 4817-4832.

    Research output: Contribution to journalArticle

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