Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The proliferation and migration of vascular smooth muscle cells (SMC) are important aspects of atherogenesis. Activated growth factor signaling in injured vessels subsequently promotes a number of intracellular events resulting in the phenotypic modulation of SMC. Here, we investigated the role of beta2-chimaerin, a non-protein kinase C phorbol ester receptor with Rac-GTPase-activating protein activity, in growth factor-stimulated SMC. The endogenous expression of beta2-chimaerin was detected in cultured human SMC by reverse transcription-polymerase chain reaction and immunohistochemistry. Next, the overexpression of HA-tagged wild-type human beta2-chimaerin was attempted using cultured rat SMC with a recombinant adenovirus (Adv-beta2-Chim). Adv-LZ encoding beta-galactosidase (LacZ) was used as the control. The proliferation of SMC stimulated by platelet-derived growth factor (PDGF-BB, 10 ng/ml), as measured by cell-counting and 5-bromo-2'deoxyuridine incorporation assay, was suppressed by infection with Adv-beta2-Chim (50-200 MOI), but not with control viruses. PDGF-induced SMC migration was inhibited by approximately 25% after infection with Adv-beta2-Chim (200 MOI) using a modified Boyden's chamber assay with a fibronectin-coated membrane. Confocal microscopy revealed that PDGF stimulation altered the sub-cellular localization of beta2-chimaerin. The administration of 12-O-tetradecanoyl phorbol 13-acetate also induced changes in the sub-cellular localization of beta2-chimaerin, which was not affected by a presence of the PKC inhibitor (GF109203X). Finally, PDGF-induced Rac1 activation was found to be inhibited in the Adv-beta2-Chim-infected cells. Thus, we demonstrated that beta2-chimaerin regulates the proliferation and migration of SMC downstream of growth factor signaling pathway via the regulation of Rac1 activity. The signaling mediated by beta2-chimaerin may play a role in the regulation of SMC phenotypes, thereby implicating human atherogenesis.
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PMID:Regulation of vascular smooth muscle proliferation and migration by beta2-chimaerin, a non-protein kinase C phorbol ester receptor. 1652 10