Signal transduction of the protective effect of insulin like growth factor-1 on adriamycin-induced apoptosis in cardiac muscle cells.
To determine whether Insulin-like growth factor (IGF-I) treatment represents a potential means of enhancing the survival of cardiac muscle cells from adriamycin (ADR)-induced cell death, the present study examined the ability of IGF-I to prevent cell death. The study was performed utilising the embryonic, rat, cardiac muscle cell line, H9C2. Incubating cardiac muscle cells in the presence of adriamycin increased cell death, as determined by MTT assay and annexin V-positive cell number. The addition of 100 ng/mL IGF-I, in the presence of adriamycin, decreased apoptosis. The effect of IGF-I on phosphorylation of PI, a substrate of phosphatidylinositol 3-kinase (PI 3-kinase) or protein kinase B (AKT), was also examined in H9C2 cardiac muscle cells. IGF-I increased the phosphorylation of ERK 1 and 2 and PKC zeta kinase. The use of inhibitors of PI 3-kinase (LY 294002), in the cell death assay, demonstrated partial abrogation of the protective effect of IGF-I. The MEK1 inhibitor-PD098059 and the PKC inhibitor-chelerythrine exhibited no effect on IGF-1-induced cell protection. In the regulatory subunit of PI3K-p85- dominant, negative plasmid-transfected cells, the IGF-1-induced protective effect was reversed. This data demonstrates that IGF-I protects cardiac muscle cells from ADR-induced cell death. Although IGF-I activates several signaling pathways that contribute to its protective effect in other cell types, only activation of PI 3-kinase contributes to this effect in H9C2 cardiac muscle cells.
Chae
Han-Jung
HJ
Department of Pharmacology, Institute of Cardiovascular Research, School of Medicine, Chonbuk National University, Jeonju 560-180, Korea.
Kim
Hyung-Ryong
HR
Bae
Jeehyeon
J
Chae
Soo-Uk
SU
Ha
Ki-Chan
KC
Chae
Soo-Wan
SW
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000633:toxicity*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D007334:Insulin-Like Growth Factor I; D004317:Doxorubicin; D020169:Caspases