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Rac1 Regulation of Surface Expression of Protease-Activated Receptor-1 and Responsiveness to Thrombin in Vascular Smooth Muscle Cells
- Source :
- Arteriosclerosis, Thrombosis, and Vascular Biology. 25:1506-1511
- Publication Year :
- 2005
- Publisher :
- Ovid Technologies (Wolters Kluwer Health), 2005.
-
Abstract
- Objective— Protease-activated receptor-1 (PAR1) mediates the thrombin-induced proliferation and hypertrophy of vascular smooth muscle cells. A role of Rac1 in the regulation of PAR1 expression was investigated. Methods and Results— Treatment with simvastatin, a hydroxy-3-methyl-glutaryl coenzyme A reductase inhibitor, for 24 hours attenuated the transient [Ca 2+ ] i elevation induced by thrombin. Immunofluorescence staining revealed that simvastatin decreased the surface expression of PAR1 in a manner dependent on protein geranylgeranylation. Introduction of a Rac1/Cdc42 inhibitory fragment but not a RhoA inhibitory fragment using a cell-penetrating peptide also attenuated the response to thrombin and decreased the surface expression of PAR1. Finally, downregulation of Rac1, but not RhoA, using an RNA interference technique attenuated the thrombin-induced [Ca 2+ ] i elevation. However, the level of PAR1 mRNA and the total amount of PAR1 protein remained unchanged. Conclusions— Here, we provide for the first time 3 lines of evidence that Rac1 plays a critical role in maintaining the surface expression of PAR1 and the responsiveness to thrombin in vascular smooth muscle cells. Rac1 is suggested to regulate the constitutive trafficking of PAR1 and thereby regulate the surface expression of PAR1.
- Subjects :
- rac1 GTP-Binding Protein
Simvastatin
medicine.medical_specialty
Vascular smooth muscle
RHOA
Protein Prenylation
Down-Regulation
Gene Expression
Biology
Muscle, Smooth, Vascular
Thrombin
Downregulation and upregulation
Internal medicine
Gene expression
medicine
Animals
Humans
Receptor, PAR-1
Protease-activated receptor
RNA, Messenger
Receptor
Aorta
Cells, Cultured
Coronary Vessels
Rats
Cell biology
Endocrinology
cardiovascular system
biology.protein
Protein prenylation
Calcium
Hydroxymethylglutaryl-CoA Reductase Inhibitors
rhoA GTP-Binding Protein
Cardiology and Cardiovascular Medicine
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 15244636 and 10795642
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Accession number :
- edsair.doi.dedup.....3608dd86499e8370b30b259803a17e51