Insulin-like growth factor I inhibits cardiomyocyte apoptosis and the underlying signal transduction pathways.
The effects of insulin-like growth factor I (IGF-I) on cardiomyocyte apoptosis induced by hypoxia in cultured neonatal rat cardiomyocyte were investigated. Primary neonatal rat cardiomyocytes were cultured in 95% N2-5% CO2 to imitate the in vivo hypoxic condition. Electron microscopic observation revealed a series of typical morphological changes characteristic of apoptosis in cardiomyocytes under the hypoxic condition. DNA gel electrophoresis showed DNA laddering in an ischemic duration-dependent manner. The hypoxia-induced cardiomyocyte apoptosis was also evidenced by flow cytometry and TUNEL assay. DNA gel electrophoresis showed that IGF-I in a dose range of 10(-9)-10(-7) mol/l could significantly prevent the hypoxia-induced cardiomyocyte apoptosis. The protective effects of IGF-I against hypoxia-induced apoptosis could also be verified by flow cytometry and TUNEL assay. A tyrosine kinase inhibitor (genistein), a MAPK inhibitor (PD-098059) and a P13 kinase inhibitor (wortmannin) could also suppress the antiapoptotic effects of IGF-I. These results suggest that IGF-I can directly alleviate the hypoxia-induced cardiomyocyte apoptosis and that the three kinase routes mentioned above may be involved in its signaling pathways.
Laboratory of Cardiovascular Physiology, Shanxi Medical University, Taiyuan, China.
H Y
HY
Sun
R R
RR
Zhao
J M
JM
Zhi
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D015180:Electrophoresis, Gel, Two-Dimensional; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005434:Flow Cytometry; D019833:Genistein / Q000494:pharmacology; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D000860:Hypoxia / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008854:Microscopy, Electron; D009206:Myocardium / Q000166:cytology / Q000648:ultrastructure; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007334:Insulin-Like Growth Factor I; D019833:Genistein; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one; D000077191:Wortmannin