RGD Reference Report - Salvage of nicotinamide adenine dinucleotide plays a critical role in the bioenergetic recovery of post-hypoxic cardiomyocytes. - Rat Genome Database

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

Authors: Gero, Domokos  Szabo, Csaba 
Citation: Gero D and Szabo C, Br J Pharmacol. 2015 Oct;172(20):4817-32. doi: 10.1111/bph.13252. Epub 2015 Oct 14.
RGD ID: 13524866
Pubmed: PMID:26218637   (View Abstract at PubMed)
PMCID: PMC4621988   (View Article at PubMed Central)
DOI: DOI:10.1111/bph.13252   (Journal Full-text)


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.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Rnf146Ratcellular response to glucose stimulus  IEP  RGD 
Rnf146Ratcellular response to hypoxia  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Rnf146  (ring finger protein 146)


Additional Information