Regulation of cardiac myocyte apoptosis by the GATA-4 transcription factor.
Apoptosis of cardiac muscle cells plays important roles in the development of various heart diseases including myocardial infarction and anthracycline-induced cardiomyopathy. Understanding the regulatory mechanisms of cardiac myocyte apoptosis and survival is important for establishing therapeutic strategies against heart disease. Our recent experiments demonstrate that the GATA-4 transcription factor not only mediates cardiac hypertrophy, but also regulates apoptosis and survival of adult cardiac muscle cells. Apoptosis induced by anthracyclines is associated with decreased expression of GATA-4, while the restoration of GATA-4 levels via ectopic expression attenuated the apoptosis. Survival factors of cardiac myocytes such as hepatocyte growth factor and endothelin-1 activate GATA-4, and this signal transduction mechanism at least in part serves to protect the heart against oxidative stress.
Suzuki
Yuichiro J
YJ
Cell & Molecular Nutrition Program, Friedman School of Nutrition Science and Policy, Jean Mayer USDA Human Nutrition Research Center on Aging, Department of Medicine, Tufts University, Boston, MA 02111, USA. yuichiro_sukuki@hotmail.com
Evans
Todd
T
D018943:Anthracyclines / Q000378:metabolism*; D017209:Apoptosis / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D019332:Endothelin-1 / Q000378:metabolism; D050991:GATA4 Transcription Factor; D005786:Gene Expression Regulation; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D006801:Humans; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism / Q000502:physiology*
D018943:Anthracyclines; D004268:DNA-Binding Proteins; D019332:Endothelin-1; D050991:GATA4 Transcription Factor; D014157:Transcription Factors; D017228:Hepatocyte Growth Factor