Extracellular regulated kinase, but not protein kinase C, is an antiapoptotic signal of insulin-like growth factor-1 on cultured cardiac myocytes.
This study aims to elucidate the signaling pathway for insulin-like growth factor-1 (IGF-1) in cultured neonatal rat cardiomyocytes and particularly the role of IGF-1 in cardiac apoptosis. IGF-1 stimulated polyphosphoinositide turnover, translocation of protein kinase C (PKC) isoforms (alpha, epsilon, and delta) from the soluble to the particulate fraction, activation of phospholipid-dependent and Ca(2+)-, phospholipid-dependent PKC, and activation of the extracellular-regulated kinase (ERK). IGF-1 attenuated sorbitol-induced cardiomyocyte viability and nuclear DNA fragmentation. These antiapoptotic effects of IGF-1 were blocked by PD-098059 (an MEK inhibitor) but not by bisindolylmaleimide I (BIM, a specific PKC inhibitor). The ERK pathway may therefore be an important component in the mechanism whereby IGF-1 exerts its antiapoptotic effect on the cardiomyocyte.
Foncea
R
R
Departamento de Bioquímica y Biología Molecular, Universidad de Chile, Santiago, 664 0750, Chile.
Gálvez
A
A
Pérez
V
V
Morales
M P
MP
Calixto
A
A
Meléndez
J
J
González-Jara
F
F
Díaz-Araya
G
G
Sapag-Hagar
M
M
Sugden
P H
PH
LeRoith
D
D
Lavandero
S
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D006868:Hydrolysis; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D009997:Osmotic Pressure; D010716:Phosphatidylinositols / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects
D004791:Enzyme Inhibitors; D005419:Flavonoids; D007527:Isoenzymes; D010716:Phosphatidylinositols; D007334:Insulin-Like Growth Factor I; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one