IGF-1 regulates apoptosis of cardiac myocyte induced by osmotic-stress.
Insulin-like growth factor-1 (IGF-1) is a natural protectant of cardiac myocytes that has been shown to improve cardiac function. The role of IGF-1 in attenuating apoptosis induced by osmotic stress (sorbitol, SOR) or by other known apoptotic stimuli (doxorubicin, angiotensin II, and serum withdrawal) was determined in cultured cardiac myocytes. After 6 h of exposure to SOR, apoptosis was initiated, concomitant with a decrease in cell survival and increases in poly-[ADP-ribose] polymerase (PARP) degradation and DNA fragmentation. These effects were maximal after 24 h. IGF-1 partially attenuated apoptosis induced by sorbitol but not that induced by angiotensin II, doxorubicin, or serum withdrawal. In cells preincubated with IGF-1 before the addition of SOR, we detected an increase in the number of viable cells, a decrease in the generation of DNA fragments on agarose gel electrophoresis and in the percentage of positive TUNEL cells, and a reduction on PARP levels. These results suggest that IGF-1 prevents apoptosis induced by osmotic stress in cardiac myocytes but not apoptosis induced by doxorubicin and angiotensin II.
Morales
M P
MP
Department of Biochemistry and Molecular Biology, University of Chile, Santiago, 6640750, Chile.
Gálvez
A
A
Eltit
J M
JM
Ocaranza
P
P
Díaz-Araya
G
G
Lavandero
S
S
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004317:Doxorubicin / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D006352:Heart Ventricles; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D009206:Myocardium / Q000166:cytology*; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley; D013012:Sorbitol / Q000494:pharmacology
D016895:Culture Media, Serum-Free; D000804:Angiotensin II; D013012:Sorbitol; D007334:Insulin-Like Growth Factor I; D004317:Doxorubicin