title: Supplementation of creatine and ribose prevents apoptosis and right ventricle hypertrophy in hypoxic hearts.
abstract: OBJECTIVE
  The simultaneous supplementation of creatine and D-ribose has been shown to reduce apoptosis in vitro in non-irreversibly injured cultured ischemic cardiomyocytes through down-regulation of the signaling mechanisms governing adenosine monophosphate-activated protein kinase (AMPK) and protein kinase B (Akt). Here, we test the hypothesis that an analogous mechanism exists in vivo when the challenge is chronic exposure to hypoxia.
  
  
  METHODS
  Five week-old mice were exposed to an atmosphere containing 10% O2 for 10 days. Mice were gavaged daily with vehicle, creatine, D-ribose or creatine + D-ribose. After sacrifice, myocardial and pulmonary tissue were harvested for structural and biochemical analyses.
  
  
  RESULTS
  Hypoxia induced right ventricle hypertrophy and left ventricle apoptosis. Both phenotypes were slightly reduced by either creatine or D-ribose, whereas the simultaneous administration of creatine + D-ribose almost completely reversed the effects of hypoxia. Furthermore, creatine + D-ribose diminished the hypoxia-induced increases in the activity of AMPK, Akt and JNK, but not of ERK. Finally, the hypoxia-induced pulmonary overexpression of endothelin-1 mRNA was markedly reduced by creatine + D-ribose.
  
  
  CONCLUSIONS
  The simultaneous administration of creatine + D-ribose confers additional cardiovascular protection with respect to that observed with either creatine or D-ribose. The mechanism stems from the AMPK and Akt signaling pathways. These findings may form the basis of a paradigm to re-energize non-irreversibly damaged cardiomyocytes, counteracting injury by triggering specific signaling pathways.
authors.affiliation: University of Milan - San Paolo, Department of Health Science, via di Rudinì 8, I-20142 Milan, Italy. michele.samaja@unimi.it.
authors.forename: Anna
authors.initials: A
authors.lastname: Caretti
authors.forename: Paola
authors.initials: P
authors.lastname: Bianciardi
authors.forename: Marina
authors.initials: M
authors.lastname: Marini
authors.forename: Provvidenza M
authors.initials: PM
authors.lastname: Abruzzo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bolotta
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: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D015153:Blotting, Western; D015687:Cell Hypoxia; D003401:Creatine / Q000008:administration & dosage* / Q000494:pharmacology; D017931:DNA Primers; D017380:Hypertrophy, Right Ventricular / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D060888:Real-Time Polymerase Chain Reaction; D012266:Ribose / Q000008:administration & dosage* / Q000494:pharmacology; D015398:Signal Transduction
chemical_list: D017931:DNA Primers; D012266:Ribose; D003401:Creatine