title: Supplementation of creatine and ribose prevents apoptosis in ischemic cardiomyocytes.
abstract: OBJECTIVE
  To alleviate ischemia-induced injury in the myocardium, a tissue that depends critically on energy-yielding processes, creatine may be used to enhance energy metabolism, whereas D-ribose may provide building blocks for ATP synthesis. We test the hypothesis that simultaneous supplementation of creatine+D-ribose protects non-irreversibly injured ischemic cardiomyocytes by reducing apoptosis.
  
  
  RESULTS
  When H9c2 cardiomyocytes were exposed to 24-h ischemia (1% O(2) with glucose deprivation), viability was severely compromised, but administration of 2.5 mM creatine + 5 mM D-ribose alleviated the fall in viability, whereas 2.5 mM creatine or 5 mM D-ribose did not. These findings correlated with up-regulation of protein kinase B (Akt) phosphorylation. Creatine+D-ribose also blunted adenosine monophosphate-activated protein kinase (AMPK) and down-regulated apoptosis by reducing caspase-3 activation and poly (ADP-ribose) polymerase (PARP) cleavage.
  
  
  CONCLUSIONS
  Simultaneous administration of creatine+D-ribose confers anti-ischemic protection that was absent when treating cardiomyocytes with either creatine or D-ribose. The involved mechanisms stem from the Akt and AMPK signaling pathways. These findings may form the basis of a paradigm whereby re-energization of non-irreversibly damaged cardiomyocytes is a critical step to counteract apoptosis.
authors.affiliation: Department of Medicine, Surgery and Dentistry, University of Milan, San Paolo Hospital, Milan, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Caretti
authors.forename: Paola
authors.initials: P
authors.lastname: Bianciardi
authors.forename: Giusy
authors.initials: G
authors.lastname: Sala
authors.forename: Carlo
authors.initials: C
authors.lastname: Terruzzi
authors.forename: Franco
authors.initials: F
authors.lastname: Lucchina
authors.forename: Michele
authors.initials: M
authors.lastname: Samaja
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003401:Creatine / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000166:cytology* / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D012266:Ribose / Q000494:pharmacology*; D015398:Signal Transduction
chemical_list: D012266:Ribose; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D000091162:AMP-Activated Protein Kinase Kinases; D003401:Creatine