title: PUMA-mediated mitochondrial apoptotic disruption by hypoxic postconditioning.
abstract: Postconditioning can reduce ischemia-reperfusion (I/R)-induced cardiomyocyte apoptosis by targeting mitochondria. p53 upregulated modulator of apoptosis (PUMA) is involved in lethal I/R injury. Here, we hypothesized that postconditioning might inhibit mitochondrial pathway-mediated cardiomyocyte apoptosis by controlling PUMA expression. The cultured neonatal rat cardiomyocytes underwent 3 h of hypoxia and 3 h of reoxygenation. Postconditioning consisted of three cycles of 5 min reoxygenation and 5 min hypoxia after prolonged hypoxia. Hypoxic postconditioning reduced the levels of PUMA mRNA and protein. Concomitantly, the loss of mitochondrial membrane potential, cytochrome c release and caspase-3 activation were decreased significantly by postconditioning. Overexpression of PUMA increased greatly not only the number of apoptotic cardiomyocytes, but also the collapse of mitochondrial membrane potential, cytochrome c release and caspase-3 activation under postconditioning condition. The data suggest that reduction of PUMA expression mediates the endogenous cardioprotective mechanisms of postconditioning by disrupting mitochondrial apoptotic pathway.
authors.affiliation: Department of Pathophysiology, Institute of Basic Medical Science, PLA General Hospital, Beijing, 100853, China, yuzlif96@163.com.
authors.forename: YuZhen
authors.initials: Y
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Guo
authors.forename: XiuHua
authors.initials: X
authors.lastname: Liu
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.forename: DanDan
authors.initials: D
authors.lastname: Song
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D015687:Cell Hypoxia; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism*; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C533952:Bbc3 protein, rat; D045304:Cytochromes c; D053148:Caspase 3