IGF-1 regulates apoptosis of cardiac myocyte induced by osmotic-stress

Insulin-like growth factor-1 (IGF-1) is a natural protectant of cardiac myo cytes that has been shown to improve cardiac function. The role of IGF-1 in attenuating apoptosis induced by osmotic stress (sorbitol, SOR) or by othe r known apoptotic stimuli (doxorubicin, angiotensin II, and serum withdrawa l) was determined in cultured cardiac myocytes. After 6 h of exposure to SO R, apoptosis was initiated, concomitant with a decrease in cell survival an d increases in poly[ADP-ribose] polymerase (PARP) degradation and DNA fragm entation. These effects were maximal after 24 h. IGF-1 partially attenuated apoptosis induced by sorbitol but not that induced by angiotensin II, doxo rubicin, or serum withdrawal. In cells preincubated with IGF-1 before the a ddition of SOR, we detected an increase in the number of viable cells, a de crease in the generation of DNA fragments on agarose gel electrophoresis an d in the percentage of positive TUNEL cells, and a reduction on PARP levels . These results suggest that IGF-1 prevents apoptosis induced by osmotic st ress in cardiac myocytes but not apoptosis induced by doxorubicin and angio tensin II. (C) 2000 Academic Press.