Supplementation of creatine and ribose prevents apoptosis and right ventricle hypertrophy in hypoxic hearts
Articolo
Data di Pubblicazione:
2013
Citazione:
Supplementation of creatine and ribose prevents apoptosis and right ventricle hypertrophy in hypoxic hearts / A. Caretti, P. Bianciardi, M. Marini, P.M. Abruzzo, A. Bolotta, C. Terruzzi, F. Lucchina, M. Samaja. - In: CURRENT PHARMACEUTICAL DESIGN. - ISSN 1381-6128. - 19:39(2013), pp. 6873-6879.
Abstract:
BACKGROUND/AIMS:
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.
CONCLUSION:
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.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Akt; AMPK; Apoptosis; Creatine; Hypoxia; Pulmonary endothelium; Ribose; Right vs left ventricle
Elenco autori:
A. Caretti, P. Bianciardi, M. Marini, P.M. Abruzzo, A. Bolotta, C. Terruzzi, F. Lucchina, M. Samaja
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