Ubiquitin carboxyl-terminal hydrolase L1, a novel deubiquitinating enzyme in the vasculature, attenuates NF-kappaB activation.
Arterioscler Thromb Vasc Biol
; 27(10): 2184-90, 2007 Oct.
Article
en En
| MEDLINE
| ID: mdl-17690318
ABSTRACT
OBJECTIVE:
We identified a ubiquitin carboxyl-terminal hydrolase L1 (UCHL1) gene, which encodes a deubiquitinating enzyme and is expressed in the vasculature, by functional screening of a human endothelial cell (EC) cDNA library. UCHL1 is expressed in neurons, and abnormalities in UCHL1 are responsible for inherited Parkinson's disease via its effects on the ubiquitin-proteasome system. Therefore, the goal of present study was to clarify the role of the UCHL1 gene in vascular remodeling by evaluating nuclear factor-kappaB (NF-kappaB) inactivation in ECs and vascular smooth muscle cells (VSMCs). METHODS ANDRESULTS:
From Northern blot and immunohistochemical analysis, the UCHL1 gene was endogenously expressed in vascular ECs, VSMCs, and brain tissue. Expression of UCHL1 was markedly increased in the neointima of the balloon-injured carotid artery and was also present in atherosclerotic lesions from human carotid arteries. Overexpression of the UCHL1 gene significantly attenuated tumor necrosis factor (TNF)-alpha-induced NF-kappaB activity in vascular cells and increased inhibitor of kappa B-alpha (IkappaB-alpha), possibly through the attenuation of IkappaB-alpha ubiquitination, leading to decreased neointima in the balloon-injured artery. In contrast, knockdown of UCHL1 by small interfering RNA resulted in increased NF-kappaB activity in VSMCs.CONCLUSIONS:
These data suggest that UCHL1 may partially attenuate vascular remodeling through inhibition of NF-kappaB activity.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Procesamiento Proteico-Postraduccional
/
FN-kappa B
/
Proteínas I-kappa B
/
Ubiquitina
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Células Endoteliales
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Ubiquitina Tiolesterasa
/
Músculo Liso Vascular
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Arterioscler Thromb Vasc Biol
Asunto de la revista:
ANGIOLOGIA
Año:
2007
Tipo del documento:
Article
País de afiliación:
Japón