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 (α, ε, and δ)...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2000-07, Vol.273 (2), p.736-744
Main Authors: Foncea, Rocío, Gálvez, Anita, Pérez, Viviana, Morales, María Paz, Calixto, Andrea, Meléndez, Jaime, González-Jara, Fabián, Díaz-Araya, Guillermo, Sapag-Hagar, Mario, Sugden, Peter H., LeRoith, Derek, Lavandero, Sergio
Format: Article
Language:English
Subjects:
Animals
apoptosis
Apoptosis - drug effects
cardiac myocytes
Cells, Cultured
Enzyme Inhibitors - pharmacology
Flavonoids - pharmacology
Hydrolysis
Insulin-Like Growth Factor I - pharmacology
insulin-like growth factor-1
Isoenzymes - antagonists & inhibitors
Isoenzymes - metabolism
Mitogen-Activated Protein Kinase Kinases - antagonists & inhibitors
Mitogen-Activated Protein Kinase Kinases - metabolism
Mitogen-Activated Protein Kinases - metabolism
Myocardium - cytology
Myocardium - metabolism
Osmotic Pressure
Phosphatidylinositols - metabolism
Protein Kinase C - antagonists & inhibitors
Protein Kinase C - metabolism
protein kinases
Rats
signal transduction
Signal Transduction - drug effects
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Summary: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 (α, ε, and δ) from the soluble to the particulate fraction, activation of phospholipid-dependent and Ca2+-, 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.
ISSN:0006-291X
1090-2104
DOI:10.1006/bbrc.2000.3008