Clitocybin B inhibits rat aortic smooth muscle cell proliferation through suppressing PDGF-Rß phosphorylation.
Vascul Pharmacol
; 56(1-2): 91-7, 2012.
Article
em En
| MEDLINE
| ID: mdl-22166585
ABSTRACT
The increased proliferation of vascular smooth muscle cells (VSMCs) in the arterial wall is a critical pathogenic factor for vascular diseases such as atherosclerosis and restenosis after angioplasty. Clitocybin B was reported to have either a potent free radical scavenging effect or effects that were isolated from the culture broth of mushroom Clitocybe aurantiaca. The present study was designed to investigate the effects of clitocybin B on VSMC proliferation and its possible molecular mechanism. Clitocybin B significantly inhibited the proliferation and the DNA synthesis of PDGF-BB-stimulated VSMCs in a concentration-dependent manner. In agreement with these findings, clitocybin B suppressed the PDGF-BB-induced progression through G0/G1 to S phase of cell cycle. Clitocybin B also down-regulated the expressions of cell cycle-related proteins, including cyclin-dependent kinase (CDK)2, cyclin E, CDK4, cyclin D1, and proliferative cell nuclear antigen in PDGF-BB-stimulated VSMCs. Clitocybin B significantly inhibited the phosphorylation of Akt, extracellular signal-regulated kinase 1/2, and phospholipase C-γ1, in the PDGF-BB signaling pathway. Clitocybin B suppressed the PDGF-Rß activation in PDGF-BB signaling cascade. These results suggested that the inhibitory effect of clitocybin B on the proliferation of VSMCs may be associated with suppressing PDGF-Rß phosphorylation. Thus, clitocybin B may be an effective antiproliferative agent for the prevention of atherosclerosis and restenosis.
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Base de dados:
MEDLINE
Assunto principal:
Aorta
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Fosforilação
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Receptor beta de Fator de Crescimento Derivado de Plaquetas
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Miócitos de Músculo Liso
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Isoindóis
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Músculo Liso Vascular
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article