Journal
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
Volume 23, Issue 4-6, Pages 295-304Publisher
KARGER
DOI: 10.1159/000218176
Keywords
Vascular smooth muscle cell; Early growth response gene (Egr-1); Platelet-derived growth factor (PDGF); Calcium; N-4-Tert-Butyl benzyl haloperidol chloride (C-3); G(1) cell-cycle regulatory proteins cyclin D1 and Cdk2; Cell-cycle inhibitory proteins p21Cip1
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Funding
- National Natural Science Foundation of China [30472028]
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Background: N-4-Tert-Butyl benzyl haloperidol chloride (C-3) was a novel calcium antagonist synthesized in our laboratory. The present study is to explore the effect of C-3 on vascular smooth muscle cell proliferation and the mechanism involved. Methods: The effects of C-3 on Ang II-induced cytosolic free Ca2+ concentration change, VSMC proliferation, the key early growth response factor 1 (Egr-1) were evaluated by laser scanning confocal microscopy, microtiter tetrazolium (MTT) proliferation assay, flow cytometry analysis, Western blot and RT-PCR analysis, respectively. An extracellular Ca2+ chelator EGTA and antisense Egr-1 oligodeoxyribonucleotides (ODNs) were used to establish the relation between Ca2+-dependent Egr-1 expression induced by Ang II and VSMC proliferation. Results: C-3 attenuated the Ang II-induced extracellular Ca2+ influx, inhibited VSMCs proliferation and arrested VSMCs in G(1)-phase. C-3 also triggered a significant reduction in PDGF-A and cyclin D1, Cdk2 along with an overexpression of p21Cip1. Antisense Egr-1 ODNs inhibited VSMCs proliferation, which was related to G1-phase arrest, due to inhibiting the expression of Egr-1 and C-3 inhibited the overexpression of Egr-1. Conclusion: Egr-1 may play a key role in Ang II-induced proliferation of VSMCs. C-3 inhibits vascular smooth muscle cell proliferation and the mechanism is involved with the inhibition of over-expression of Egr-1. Copyright (C) 2009 S. Karger AG, Basel
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