Activation of PKC{beta}{sub II} and PKC{theta} is essential for LDL-induced cell proliferation of human aortic smooth muscle cells via Gi-mediated Erk1/2 activation and Egr-1 upregulation
- Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yuseong, Daejeon (Korea, Republic of)
- Bio-Evaluation Center, KRIBB, Yuseong, Daejeon (Korea, Republic of)
- Therapeutic Antibody Research Center, KRIBB, Yuseong, Daejeon (Korea, Republic of)
- Department of Pharmacy, Chungnam National University, Yuseong, Daejeon (Korea, Republic of)
- Department of Obstetrics and Gynecology, Inha University Hospital, Incheon (Korea, Republic of)
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 PKC{beta}{sub II} and PKC{theta} from cytosol to plasma membrane, and inhibition of PKC{beta}{sub II} and PKC{theta} decreased LDL effects via the deactivation of Erk1/2. Moreover, pertussis toxin, but not cholera toxin or heparin, inhibited LDL-induced translocation of PKC{beta}{sub II} and PKC{theta}, 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 PKC{beta}{sub II} and PKC{theta}. Inhibition of PKC{beta}{sub II} or PKC{theta}, 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 PKC{theta} in VSMC proliferation is unique.
- OSTI ID:
- 21043674
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 368, Issue 1; Other Information: DOI: 10.1016/j.bbrc.2008.01.050; PII: S0006-291X(08)00090-9; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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