RhoA has been shown to play a major role in vascular processes and acetylsalicylic acid (aspirin) is known to exert a cytoprotective effect via multiple mechanisms. In the present study, we aimed at investigating the effect of aspirin on RhoA expression under a stress state in rat VSMCs (vascular smooth muscle cells) and the underlying mechanisms. The expression of iNOS (inducible nitric oxide synthase) and iNOS activity as well as NO concentration was significantly promoted by LPS (lipopolysaccharide) accompanying the elevation of RhoA expression, which was blocked by the addition of the iNOS inhibitor L-NIL [L-N6-(1-iminoethyl)lysine dihydrochloride]. Aspirin (30 μM) significantly attenuated the elevation of RhoA, while indomethacin and salicylate had no similar effect. The sGC (soluble guanylate cyclase) inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) showed the same effect as aspirin in down-regulating RhoA but was reversed by the addition of the cGMP analogue 8-Br-PET-cGMP (β-phenyl-1,N2-ethano-8-bromoguanosine 3′,5′-cyclic monophosphorothioate). 8-Br-PET-cGMP solely enhanced the RhoA expression that was abrogated by preincubation with aspirin. Degradation analysis indicated that aspirin enhanced the protein degradation rate of RhoA and GDP-bound RhoA seemed to be more susceptible to aspirin-enhanced degradation compared with the GTP-bound form. Our results indicate that aspirin attenuates the LPS-induced overexpression of RhoA both by inhibiting new synthesis and accelerating protein degradation, which may help elucidate the multiple beneficial effects of aspirin.
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Research Article|
November 21 2011
Acetylsalicylic acid regulates overexpressed small GTPase RhoA in vascular smooth muscle cells through prevention of new synthesis and enhancement of protein degradation
Dong-Bo Li;
Dong-Bo Li
*Institute of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, People's Republic of China
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Zhi-Xuan Fu;
Zhi-Xuan Fu
†Key Laboratory of Cancer Prevention and Intervention (China National Ministry of Education), The Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou 310009, People's Republic of China
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Shu-Qin Ruan;
Shu-Qin Ruan
†Key Laboratory of Cancer Prevention and Intervention (China National Ministry of Education), The Second Affiliated Hospital, School of Medicine, Zhejiang University, 88 Jiefang Road, Hangzhou 310009, People's Republic of China
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Shen-Jiang Hu;
Shen-Jiang Hu
1
*Institute of Cardiology, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, People's Republic of China
1To whom correspondence should be addressed (email s0hu0001@hotmail.com).
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Xia Li
Xia Li
‡Department of Neurology, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, People's Republic of China
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Publisher: Portland Press Ltd
Received:
April 18 2011
Revision Received:
June 21 2011
Accepted:
July 14 2011
Accepted Manuscript online:
July 14 2011
Online ISSN: 1573-4935
Print ISSN: 0144-8463
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biosci Rep (2012) 32 (2): 153–160.
Article history
Received:
April 18 2011
Revision Received:
June 21 2011
Accepted:
July 14 2011
Accepted Manuscript online:
July 14 2011
Citation
Dong-Bo Li, Zhi-Xuan Fu, Shu-Qin Ruan, Shen-Jiang Hu, Xia Li; Acetylsalicylic acid regulates overexpressed small GTPase RhoA in vascular smooth muscle cells through prevention of new synthesis and enhancement of protein degradation. Biosci Rep 1 April 2012; 32 (2): 153–160. doi: https://doi.org/10.1042/BSR20110050
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