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.
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.
Son
Dong Ju
DJ
College of Pharmacy and CBITRC, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Kang
Jun
J
Kim
Tack Joong
TJ
Song
Ho-Sueb
HS
Sung
Ki-Joong
KJ
Yun
Do Young
DY
Hong
Jin Tae
JT
D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects; D001514:Bee Venoms / Q000494:pharmacology*; D002478:Cells, Cultured; D008555:Melitten / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D014443:Tyrosine / Q000378:metabolism
D001514:Bee Venoms; D008555:Melitten; D014443:Tyrosine; D020797:Receptor, Platelet-Derived Growth Factor beta