کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2792781 1155085 2012 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cullin-3 Regulates Vascular Smooth Muscle Function and Arterial Blood Pressure via PPARγ and RhoA/Rho-Kinase
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی علوم غدد
پیش نمایش صفحه اول مقاله
Cullin-3 Regulates Vascular Smooth Muscle Function and Arterial Blood Pressure via PPARγ and RhoA/Rho-Kinase
چکیده انگلیسی

SummaryDominant-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.

Graphical AbstractFigure optionsDownload high-quality image (266 K)Download as PowerPoint slideHighlights
► Interference with PPARγ in smooth muscle increases RhoA/Rho-kinase activity
► RhoBTB1 is a PPARγ target gene that acts in concert with Cullin-3
► Knockdown of Cullin-3 or inhibition of cullin-RING ligase activity increases RhoA
► Cullin-RING ligase inhibition increases vascular contraction and arterial pressure

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 16, Issue 4, 3 October 2012, Pages 462–472
نویسندگان
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