کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2006624 1066347 2010 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Urotensin II induction of adult cardiomyocytes hypertrophy involves the Akt/GSK-3β signaling pathway
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Urotensin II induction of adult cardiomyocytes hypertrophy involves the Akt/GSK-3β signaling pathway
چکیده انگلیسی

Urotensin II (UII) a potent vasoactive peptide is upregulated in the failing heart and promotes cardiomyocytes hypertrophy, in particular through mitogen-activated protein kinases. However, the regulation by UII of GSK-3β, a recognized pivotal signaling element of cardiac hypertrophy has not yet been documented. We therefore investigated in adult cardiomyocytes, if UII phosphorylates GSK-3β and Akt, one of its upstream regulators and stabilizes β-catenin, a GSK-3β dependent nuclear transcriptional co-activator. Primary cultures of adult rat cardiomyocytes were stimulated for 48 h with UII. Cell size and protein/DNA contents were determined. Phosphorylated and total forms of Akt, GSK-3β and the total amount of β-catenin were quantified by western blot. The responses of cardiomyocytes to UII were also evaluated after pretreatment with the chemical phosphatidyl-inositol-3-kinase inhibitor, LY294002, and urantide, a competitive UII receptor antagonist. UII increased cell size and the protein/DNA ratio, consistent with a hypertrophic response. UII also increased phosphorylation of Akt and its downstream target GSK-3β. β-Catenin protein levels were increased. All of these effects of UII were prevented by LY294002, and urantide. The UII-induced adult cardiomyocytes hypertrophy involves the Akt/GSK-3β signaling pathways and is accompanied by the stabilization of the β-catenin. All these effects are abolished by competitive inhibition of the UII receptor, consistent with new therapeutic perspectives for heart failure treatment.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Peptides - Volume 31, Issue 7, July 2010, Pages 1326–1333
نویسندگان
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