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. 2007 Aug;70(15-16):1350-5.
doi: 10.1080/15287390701428689.

Melittin, a Major Bioactive Component of Bee Venom Toxin, Inhibits PDGF Receptor Beta-Tyrosine Phosphorylation and Downstream Intracellular Signal Transduction in Rat Aortic Vascular Smooth Muscle Cells

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Melittin, a Major Bioactive Component of Bee Venom Toxin, Inhibits PDGF Receptor Beta-Tyrosine Phosphorylation and Downstream Intracellular Signal Transduction in Rat Aortic Vascular Smooth Muscle Cells

Dong Ju Son et al. J Toxicol Environ Health A. .

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)-kappaB 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 (Rbeta) and its downstream intracellular signal transduction. When combined with PDGF-Rbeta inhibitor, melittin exhibited a synergic inhibitory effect on PDGF-BB-induced rat aortic VSMC proliferation. In addition, melittin inhibited PDGF-Rbeta phosphorylation in a concentration-dependent manner. Accordingly, the downstream signal transduction of PDGF-Rbeta, such as ERK1/2, Akt, and PLCgamma1 phosphorylation, was also inhibited by melittin in the same manner. These findings suggest that, in addition to suppressing NF-kappaB activation, the antiproliferative effect of melittin in VSMC may be mediated, at least in part, by the inhibition of PDGF-Rbeta tyrosine phosphorylation and its downstream intracellular signal transduction.

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