title: Salvage of nicotinamide adenine dinucleotide plays a critical role in the bioenergetic recovery of post-hypoxic cardiomyocytes.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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).
  
  
  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
  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.
authors.affiliation: Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Domokos
authors.initials: D
authors.lastname: Gero
authors.affiliation: Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Csaba
authors.initials: C
authors.lastname: Szabo
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D004734:Energy Metabolism; D005947:Glucose / Q000172:deficiency; D006861:Hydrogen Peroxide / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000378:metabolism*; D009243:NAD / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013481:Superoxides / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism
chemical_list: D016877:Oxidants; D009243:NAD; D013481:Superoxides; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; C000603303:RNF146 protein, rat; D044767:Ubiquitin-Protein Ligases; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D005947:Glucose