Activation of PKCbeta(II) and PKCtheta is essential for LDL-induced cell proliferation of human aortic smooth muscle cells via Gi-mediated Erk1/2 activation and Egr-1 upregulation.
Biochem Biophys Res Commun
; 368(1): 126-31, 2008 Mar 28.
Article
em En
| MEDLINE
| ID: mdl-18211822
ABSTRACT
Native LDL may be a mitogenic stimulus of VSMC proliferation in lesions where endothelial disruption occurs. Recent studies have demonstrated that the mitogenic effects of LDL are accompanied by Erk1/2 activation via an unknown G-protein-coupled receptor (GPCR). In this article, we report that LDL translocated PKCbeta(II) and PKCtheta from cytosol to plasma membrane, and inhibition of PKCbeta(II) and PKCtheta decreased LDL effects via the deactivation of Erk1/2. Moreover, pertussis toxin, but not cholera toxin or heparin, inhibited LDL-induced translocation of PKCbeta(II) and PKCtheta, suggesting that Gi protein plays a role in LDL effects. Of LPA, S1P, and LDL, whose signaling is conveyed via Gi/o proteins, only LDL induced translocation of PKCbeta(II) and PKCtheta. Inhibition of PKCbeta(II) or PKCtheta, as well as of Erk1/2 and GPCR, decreases LDL-induced upregulation of Egr-1, which is critical for cell proliferation. This is the first report, to our knowledge, that the participation of PKCtheta in VSMC proliferation is unique.
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Base de dados:
MEDLINE
Assunto principal:
Proteína Quinase C
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Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP
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Miócitos de Músculo Liso
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MAP Quinases Reguladas por Sinal Extracelular
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Proteína 1 de Resposta de Crescimento Precoce
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Isoenzimas
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LDL-Colesterol
Idioma:
En
Ano de publicação:
2008
Tipo de documento:
Article