| Cullin-3 regulates vascular smooth muscle function and arterial blood pressure via PPARγ and RhoA/Rho-kinase. | |
| | |
MedLine Citation:
|
PMID: 23040068 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Dominant-negative (DN) mutations in the nuclear hormone receptor peroxisome proliferator-activated receptor-γ (PPARγ) cause hypertension by an unknown mechanism. Hypertension and vascular dysfunction are recapitulated by expression of DN PPARγ specifically in vascular smooth muscle of transgenic mice. DN PPARγ increases RhoA and Rho-kinase activity, and inhibition of Rho-kinase restores normal reactivity and reduces arterial pressure. RhoBTB1, a component of the Cullin-3 RING E3 ubiquitin ligase complex, is a PPARγ target gene. Decreased RhoBTB1, Cullin-3, and neddylated Cullin-3 correlated with increased levels of the Cullin-3 substrate RhoA. Knockdown of Cullin-3 or inhibition of cullin-RING ligase activity in aortic smooth muscle cells increased RhoA. Cullin-RING ligase inhibition enhanced agonist-mediated contraction in aortic rings from normal mice by a Rho-kinase-dependent mechanism, and it increased arterial pressure in vivo. We conclude that Cullin-3 regulates vascular function and arterial pressure, thus providing a mechanistic link between mutations in Cullin-3 and hypertension in humans. |
| | |
Authors:
|
Christopher J Pelham; Pimonrat Ketsawatsomkron; Séverine Groh; Justin L Grobe; Willem J de Lange; Stella-Rita C Ibeawuchi; Henry L Keen; Eric T Weatherford; Frank M Faraci; Curt D Sigmund |
Related Documents
:
|
6340528 - Neurohumoral mechanisms in acute aortic coarctation in conscious and anesthetized dogs. 22522418 - A surgical technique for a terminal intracranial hypertension model in pigs. 2829598 - The antihypertensive contribution of bradykinin as assessed by a specific bradykinin an... 16081858 - Role of the bloodstream impacting force and the local pressure elevation in the rupture... 14557278 - Effect of hypertension and hypertension-glucose intolerance on myocardial ischemic injury. 19996138 - Pulse pressure and long-term survival after coronary artery bypass graft surgery. |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Cell metabolism Volume: 16 ISSN: 1932-7420 ISO Abbreviation: Cell Metab. Publication Date: 2012 Oct |
Date Detail:
|
Created Date: 2012-10-08 Completed Date: 2013-03-07 Revised Date: 2013-04-16 |
Medline Journal Info:
|
Nlm Unique ID: 101233170 Medline TA: Cell Metab Country: United States |
Other Details:
|
Languages: eng Pagination: 462-72 Citation Subset: IM |
Copyright Information:
|
Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
|
Department of Pharmacology, Roy J. and Lucille A. Carver College of Medicine, University of Iowa, Iowa City, Iowa 52242, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Blood Pressure / physiology Cullin Proteins / antagonists & inhibitors, genetics, metabolism* HEK293 Cells Humans Mice Mice, Transgenic Muscle, Smooth, Vascular / metabolism* PPAR gamma / antagonists & inhibitors, metabolism* RNA Interference RNA, Small Interfering / metabolism Transfection rho-Associated Kinases / metabolism* rhoA GTP-Binding Protein / metabolism* |
| Grant Support | |
ID/Acronym/Agency:
|
HL038901/HL/NHLBI NIH HHS; HL048058/HL/NHLBI NIH HHS; HL061446/HL/NHLBI NIH HHS; HL062984/HL/NHLBI NIH HHS; HL084207/HL/NHLBI NIH HHS; HL098276/HL/NHLBI NIH HHS; K99 HL098276/HL/NHLBI NIH HHS; NS024621/NS/NINDS NIH HHS; P01 HL062984/HL/NHLBI NIH HHS; P01 HL084207/HL/NHLBI NIH HHS; P01 NS024621/NS/NINDS NIH HHS; R00 HL098276/HL/NHLBI NIH HHS; R01 HL061446/HL/NHLBI NIH HHS; R37 HL048058/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Cul3 protein, mouse; 0/Cullin Proteins; 0/PPAR gamma; 0/RNA, Small Interfering; EC 2.7.11.1/rho-Associated Kinases; EC 3.6.5.2/rhoA GTP-Binding Protein |
| Comments/Corrections | |
Comment In:
|
Cell Metab. 2012 Oct 3;16(4):410-1
[PMID:
23040065
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Human ? cell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated...
Next Document: IRE1?-XBP1s induces PDI expression to increase MTP activity for hepatic VLDL assembly and lipid home...