Rac1 regulation of surface expression of protease-activated receptor-1 and responsiveness to thrombin in vascular smooth muscle cells

Tatsuya Yufu, Katsuya Hirano, Dan Bi, Mayumi Hirano, Junji Nishimura, Yukihide Iwamoto, Hideo Kanaide

研究成果: ジャーナルへの寄稿記事

17 引用 (Scopus)

抄録

Objective-Protease-activated receptor-1 (PAR1) mediates the thrombin-induced proliferation and hypertrophy of vascular smooth muscle cells. A role of Racl 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+]1 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 [Ca2+] 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.

元の言語英語
ページ(範囲)1506-1511
ページ数6
ジャーナルArteriosclerosis, thrombosis, and vascular biology
25
発行部数7
DOI
出版物ステータス出版済み - 7 1 2005
外部発表Yes

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PAR-1 Receptor
Vascular Smooth Muscle
Thrombin
Smooth Muscle Myocytes
Simvastatin
Protein Prenylation
Cell-Penetrating Peptides
RNA Interference
Hypertrophy
Fluorescent Antibody Technique
Oxidoreductases
Down-Regulation
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

これを引用

Rac1 regulation of surface expression of protease-activated receptor-1 and responsiveness to thrombin in vascular smooth muscle cells. / Yufu, Tatsuya; Hirano, Katsuya; Bi, Dan; Hirano, Mayumi; Nishimura, Junji; Iwamoto, Yukihide; Kanaide, Hideo.

:: Arteriosclerosis, thrombosis, and vascular biology, 巻 25, 番号 7, 01.07.2005, p. 1506-1511.

研究成果: ジャーナルへの寄稿記事

Yufu, Tatsuya ; Hirano, Katsuya ; Bi, Dan ; Hirano, Mayumi ; Nishimura, Junji ; Iwamoto, Yukihide ; Kanaide, Hideo. / Rac1 regulation of surface expression of protease-activated receptor-1 and responsiveness to thrombin in vascular smooth muscle cells. :: Arteriosclerosis, thrombosis, and vascular biology. 2005 ; 巻 25, 番号 7. pp. 1506-1511.
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