title: PUMA mediates the apoptotic signal of hypoxia/reoxygenation in cardiomyocytes through mitochondrial pathway.
abstract: P53 upregulated modulator of apoptosis (PUMA) plays an important role in mediating cell death. However, the role of PUMA in cardiomyocyte death induced by hypoxia/reoxygenation (H/R) and its molecular mechanism still remain enigmatic. Here, we used the in vitro model to elucidate the effects of PUMA on H/R-induced cardiomyocyte apoptosis as well as the underlying mechanisms. We reported that H/R could upregulate the expression of PUMA accompanied by the elevation of cardiomyocyte apoptosis. Interestingly, inhibition of endogenous PUMA expression by PUMA siRNA or p53 inhibitor repressed H/R-induced cardiomyocyte apoptosis. Furthermore, we found H/R stimulated the associations of PUMA apoptosis repressor with caspase recruitment domain (ARC) and consequently attenuated the associations of ARC with caspase 8, resulting in caspase 8 activation. Also, H/R stimulated cytochrome C release and caspase 3 activation. However, these stimulating effects of H/R disappeared upon knockdown of endogenous PUMA. Our data reveal that PUMA participates in H/R-triggered cardiomyocyte apoptosis by interfering with mitochondrial pathway.
authors.affiliation: Department of Pathophysiology, Institute of Basic Medical Science, PLA General Hospital, Beijing, China. yuzlif96@yahoo.com.cn
authors.forename: Yuzhen
authors.initials: Y
authors.lastname: Li
authors.forename: Xiuhua
authors.initials: X
authors.lastname: Liu
authors.forename: Fei
authors.initials: F
authors.lastname: Rong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D052160:Benzothiazoles / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D002478:Cells, Cultured; D045304:Cytochromes c / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008929:Mitochondria, Heart / Q000502:physiology*; D009124:Muscle Proteins / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*; D014050:Toluene / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D051017:Apoptosis Regulatory Proteins; D052160:Benzothiazoles; D009124:Muscle Proteins; C491788:Nol3 protein, rat; D014050:Toluene; D045304:Cytochromes c; C121565:pifithrin; C505528:Casp8 protein, rat; D053148:Caspase 3; D053181:Caspase 8