Regulators of apoptosis in the heart: a matter of life and death.
Programmed cell death or apoptosis is an active physiological process that permits the removal of unwanted or damaged cells from the body through an intrinsic cell-suicide program. Apoptosis is characterized by condensation of the nucleus and cytoplasm without loss of membrane integrity. The occurrence of apoptosis in the vasculature and myocardium has recently been described. Inappropriate loss of myocardial cells is suggested to contribute to conduction defects and ventricular remodelling after injury. The molecular mechanisms that regulate programmed cell death in cardiac muscle cells are poorly defined. However, recent evidence has suggested that specific genes can either provoke or prevent apoptosis. In this regard, the tumour suppressor protein p53 has been proposed to mediate apoptosis, while the Bcl-2 protein prevents it. Prevention of apoptosis in the heart is potentially of significant therapeutic value given the limited capacity of the heart to repair itself after injury. This study determined that the expression of p53 in ventricular myocytes is sufficient to trigger apoptosis. Moreover, p53 results in a significant increase in the expression of the death-promoting protein Bax. Importantly, the antiapoptotic factor Bcl-2 is sufficient to prevent p53-mediated apoptosis and p53-dependent transcription of Bax in ventricular myocytes. The data substantiate a role for p53 and Bcl-2 as crucial regulators of apoptosis in the heart.
Kirshenbaum
L A
LA
Institute of Cardiovascular Sciences, St Boniface General Hospital Research Centre, University of Manitoba, Winnipeg. Lorrie@SBRC.umanitoba.ca
D017209:Apoptosis / Q000235:genetics*; D016757:Death, Sudden, Cardiac; D005260:Female; D015870:Gene Expression; D005809:Genes, Regulator / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics*; D006331:Heart Diseases / Q000235:genetics* / Q000473:pathology; D006352:Heart Ventricles / Q000166:cytology; D006801:Humans; D008297:Male; D009206:Myocardium / Q000473:pathology*