Abstract
Studies previously reported that melittin, a major bioactive component of bee venom, inhibits vascular smooth muscle cell (VSMC) proliferation through suppression of nuclear factor (NF)-κB and Akt activation and through enhancement of proapoptotic protein expression. In this study, the effects of melittin were investigated on the tyrosine phosphorylation of platelet-derived growth factor (PDGF) beta receptor (Rβ) and its downstream intracellular signal transduction. When combined with PDGF-Rβ inhibitor, melittin exhibited a synergic inhibitory effect on PDGF-BB-induced rat aortic VSMC proliferation. In addition, melittin inhibited PDGF-Rβ phosphorylation in a concentration-dependent manner. Accordingly, the downstream signal transduction of PDGF-Rβ, such as ERK1/2, Akt, and PLCγ1 phosphorylation, was also inhibited by melittin in the same manner. These findings suggest that, in addition to suppressing NF-κB activation, the antiproliferative effect of melittin in VSMC may be mediated, at least in part, by the inhibition of PDGF-Rβ tyrosine phosphorylation and its downstream intracellular signal transduction.
This work was supported by the Regional Research Centers Program of the Ministry of Education & Human Resources Development and by grant R01-2006-10145-0 from the Korea Science and Engineering Foundation (KOSEF) in Korea.