Melittin has an inhibitory effect on TNF-alpha-induced migration of human aortic smooth muscle cells by blocking the MMP-9 expression

Title
Melittin has an inhibitory effect on TNF-alpha-induced migration of human aortic smooth muscle cells by blocking the MMP-9 expression
Author(s)
장현욱정윤정[정윤정]조현지[조현지]Key Hwang[Key Hwang]이이선[이이선]박환규[박환규]채정윤[채정윤]한상미[한상미]김철호[김철호]문성관[문성관]김운재[김운재]최융현[최융현]장영채[장영채]
Keywords
NF-KAPPA-B; MATRIX-METALLOPROTEINASE EXPRESSION; BEE VENOM TOXIN; MATRIX-METALLOPROTEINASE-9 EXPRESSION; ENDOTHELIAL-CELLS; ARTERIAL INJURY; ACTIVATION; RAT; PHOSPHORYLATION; PROLIFERATION
Issue Date
201211
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Citation
FOOD AND CHEMICAL TOXICOLOGY, v.50, no.11, pp.3996 - 4002
Abstract
Matrix metalloproteinases-9 (MMP-9) plays an important role in the pathogenesis of atherosclerosis and migration of vascular smooth muscle cells (VSMCs) after an arterial injury. In this study, we investigated the potential molecular mechanisms underlying the anti-atheroscleroic effects of melittin, a major component of bee venom, in human aortic smooth muscle cells (HASMCs). Melttin significantly suppressed MMP-9 and MMP-2 secretion, as well as TNF-alpha-induced MMP-9 expression in the HASMCs. In addition, we found that the inhibitory effects of melittin. on TNF-alpha-induced MMP-9 protein expression are associated with the inhibition of MMP-9 transcription levels. Mechanistically, Melittin suppressed TNF-alpha-induced MMP-9 activity by inhibiting the phosphorylation of p38 and ERK1/2, but did not affect the phosphorylation of JNK and Akt. Reporter gene and western blotting assays showed that melittin inhibits MMP-9 transcriptional activity by blocking the activation of NF-kappa B via I kappa B alpha signaling pathway. Moreover, the matrigel migration assay showed that melittin reduced TNF-alpha-induced HASMC migration. These results suggest that melittin suppresses TNF-alpha-induced HASMC migration through the selective inhibition of MMP-9 expression and provide a novel role of melittin in the anti-atherosclerotic action. (C) 2012 Elsevier Ltd. All rights reserved.
URI
http://hdl.handle.net/YU.REPOSITORY/26954http://dx.doi.org/10.1016/j.fct.2012.08.026
ISSN
0278-6915
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약학대학 > 약학부 > Articles
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