title: Insulin-like growth-factor-1-induced PKB signaling and Egr-1 expression is inhibited by curcumin in A-10 vascular smooth muscle cells.
abstract: Insulin-like growth factor 1 (IGF-1) is a mitogenic factor that stimulates the signaling pathways responsible for inducing hypertrophic and proliferative responses in vascular smooth muscle cells (VSMC). We have previously demonstrated that IGF-1 receptor (IGF-1R) plays a key role in transducing the hypertrophic and proliferative responses of angiotensin II (Ang-II) and endothelin-1 (ET-1). Curcumin, a polyphenolic compound derived from the spice turmeric is known to possess antiproliferative properties and exerts vasculoprotective effects. However, the ability of curcumin to modulate IGF-1-induced signaling responses in VSMC remains to be investigated. In this study, we determined the effect of curcumin on IGF-1-induced phosphorylation of protein kinase B (PKB), glycogen synthase kinase-3β (GSK-3β), and IGF-1R in VSMC. Curcumin inhibited IGF-1-induced phosphorylation of PKB and GSK-3β as well as the IGF-1R β subunit in a dose-dependent fashion. In addition, IGF-1-induced expression of early growth response protein 1 (Egr-1) which plays a pathogenic role in vascular dysfunctions, was also attenuated by curcumin. In conclusion, these results indicate that curcumin is a potent inhibitor of key components of the IGF-1-induced mitogenic and proliferative signaling system in VSMC, and suggest that curcumin-induced attenuation of these signaling components may constitute a potential mechanism for its vasculoprotective effects.
authors.affiliation: Laboratory of Cell Signaling, Montreal Diabetes Research Center, Research Centre of Centre Hospitalier de l'Université de Montréal-Angus Campus, and Department of Medicine, Université de Montréal, Montréal, QC, Canada.
authors.forename: Viktoria
authors.initials: V
authors.lastname: Youreva
authors.forename: Georgia
authors.initials: G
authors.lastname: Kapakos
authors.forename: Ashok K
authors.initials: AK
authors.lastname: Srivastava
mesh_terms: D000818:Animals; D002460:Cell Line; D003474:Curcumin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D051766:Early Growth Response Protein 1 / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000096:biosynthesis*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; C548904:insulin-like growth factor-1, rat; D007334:Insulin-Like Growth Factor I; D051057:Proto-Oncogene Proteins c-akt; D003474:Curcumin