title: Ubiquitin carboxyl-terminal hydrolase L1, a novel deubiquitinating enzyme in the vasculature, attenuates NF-kappaB activation.
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).
  
  
  RESULTS
  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.
authors: Department of Geriatric Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita 565-0871, Japan.
authors: Yoichi
authors: Y
authors: Takami
authors: Hironori
authors: H
authors: Nakagami
authors: Ryuichi
authors: R
authors: Morishita
authors: Tomohiro
authors: T
authors: Katsuya
authors: Tai-Xing
authors: TX
authors: Cui
authors: Tomonaga
authors: T
authors: Ichikawa
authors: Yukihiro
authors: Y
authors: Saito
authors: Hiroki
authors: H
authors: Hayashi
authors: Yasushi
authors: Y
authors: Kikuchi
authors: Tomoyuki
authors: T
authors: Nishikawa
authors: Yoshichika
authors: Y
authors: Baba
authors: Osamu
authors: O
authors: Yasuda
authors: Hiromi
authors: H
authors: Rakugi
authors: Toshio
authors: T
authors: Ogihara
authors: Yasufumi
authors: Y
authors: Kaneda
mesh_terms: D000818:Animals; D020212:Carotid Artery Injuries / Q000201:enzymology / Q000209:etiology / Q000378:metabolism; D016893:Carotid Stenosis / Q000201:enzymology; D002404:Catheterization / Q000009:adverse effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000201:enzymology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000201:enzymology / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D013997:Time Factors; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606206:Nfkbia protein, rat; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha; C482860:UCHL1 protein, human; D025801:Ubiquitin; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; C489034:UCHL1 protein, rat; D043222:Ubiquitin Thiolesterase