Caveolin-1 down-regulation inhibits insulin-like growth factor-I receptor signal transduction in H9C2 rat cardiomyoblasts.
Caveolin (Cav)-1, the major caveolar protein, directly interacts with IGF-I receptor (IGF-IR) and its intracellular substrates. To determine the role of Cav-1 in IGF-IR signaling, we transfected H9C2 cells with small interfering RNA specific for Cav-1-siRNA. The selective down-regulation of Cav-1 (90%) was associated with a smaller reduction of Cav-2, whereas Cav-3 expression was unaffected. A significant reduction of IGF-IR tyrosine phosphorylation in Cav-1-siRNA H9C2 cells was found compared with H9C2 control cells (Ctr-siRNA). The reduced IGF-IR autophosphorylation resulted in a decrease of insulin receptor substrate-1, Shc, and Akt activation. In addition, in Cav-1-siRNA H9C2 cells, IGF-I did not prevent apoptosis, suggesting that Cav-1 is required to mediate the antiapoptotic effect of IGF-I in cardiomyoblasts. The down-regulation of Cav-1 decreased IGF-IR activation and affected the ability of IGF-I to prevent apoptosis after serum withdrawal also in human umbilical vein endothelial cells. These results demonstrate that: 1) Cav-1 down-regulation negatively affects IGF-IR tyrosine phosphorylation; 2) this effect causes a reduced activation of insulin receptor substrate-1, Shc, and Akt; and 3) Cav-1 is involved in IGF-IR antiapoptotic signaling after serum deprivation.
Salani
Barbara
B
Department of Endocrinology and Medicine, Viale Benedetto XV, 6, University of Genova, 5-16132, Genova, Italy.
Briatore
Lucia
L
Garibaldi
Silvano
S
Cordera
Renzo
R
Maggi
Davide
D
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051242:Caveolin 1 / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D015536:Down-Regulation / Q000502:physiology; D042783:Endothelial Cells / Q000166:cytology; D006801:Humans; D032386:Myoblasts, Cardiac / Q000166:cytology* / Q000378:metabolism*; D010766:Phosphorylation; D034741:RNA, Small Interfering; D051381:Rats; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D014471:Umbilical Veins / Q000166:cytology
D051242:Caveolin 1; D034741:RNA, Small Interfering; D017526:Receptor, IGF Type 1