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 |
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Authors: | Heo Kyung-Sun Kim Dong-Uk Kim Lila Nam Miyoung Baek Seung-Tae Park Song-Kyu Park Youngwoo Myung Chang-Seon Hwang Sung-Ook Hoe Kwang-Lae |
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Institution: | a Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong, Daejeon, Republic of Korea b Bio-Evaluation Center, KRIBB, Yuseong, Daejeon, Republic of Korea c Therapeutic Antibody Research Center, KRIBB, Yuseong, Daejeon, Republic of Korea d Department of Pharmacy, Chungnam National University, Yuseong, Daejeon, Republic of Korea e Department of Obstetrics and Gynecology, Inha University Hospital, Incheon, Republic of Korea |
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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 PKCβII and PKCθ from cytosol to plasma membrane, and inhibition of PKCβII and PKCθ decreased LDL effects via the deactivation of Erk1/2. Moreover, pertussis toxin, but not cholera toxin or heparin, inhibited LDL-induced translocation of PKCβII and PKCθ, 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 PKCβII and PKCθ. Inhibition of PKCβII or PKCθ, 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 PKCθ in VSMC proliferation is unique. |
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Keywords: | Egr-1 Erk1/2 MAPK GPCR Low-density lipoprotein PKC Smooth muscle cell |
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