Supplementation of Creatine and Ribose Prevents Apoptosis in Ischemic Cardiomyocytes

Cellular Physiology and Biochemistry

关键词: AMPK;    Akt;    Creatine;    Ribose;    Cardiomyocytes;    Ischemia;   

DOI  :  10.1159/000323992

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

Background/Aims. 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% O₂ 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.

【 授权许可】

CC BY-NC-ND