http://www.cnr.it/ontology/cnr/individuo/prodotto/ID193996
P300/CBP associated factor regulates nitroglycerin-dependent arterial relaxation by N(?)-lysine acetylation of contractile proteins (Articolo in rivista)
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- P300/CBP associated factor regulates nitroglycerin-dependent arterial relaxation by N(?)-lysine acetylation of contractile proteins (Articolo in rivista) (literal)
- Anno
- 2012-01-01T00:00:00+01:00 (literal)
- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#doi
- 10.1161/ATVBAHA.112.254011 (literal)
- Alternative label
Claudia Colussi; Alessandro Scopece; Serena Vitale; Francesco Spallotta; Stefania Mattiussi; Jessica Rosati; Barbara Illi; Antonello Mai; Sabrina Castellano; Gianluca Sbardella; Antonella Farsetti; Maurizio C. Capogrossi; Carlo Gaetano (2012)
P300/CBP associated factor regulates nitroglycerin-dependent arterial relaxation by N(?)-lysine acetylation of contractile proteins
in Arteriosclerosis, thrombosis, and vascular biology
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- Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
- Claudia Colussi; Alessandro Scopece; Serena Vitale; Francesco Spallotta; Stefania Mattiussi; Jessica Rosati; Barbara Illi; Antonello Mai; Sabrina Castellano; Gianluca Sbardella; Antonella Farsetti; Maurizio C. Capogrossi; Carlo Gaetano (literal)
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- Laboratorio di PatologiaVascolare, Istituto Dermopatico dell'Immacolata, Roma, Italy (C.C., S.V., J.R., M.C.C.); Laboratorio di Biologia Vascolare e Medicina Rigenerativa, Istituto Cardiologico Monzino, Milano, Italy (A.S., F.S.); Laboratorio Acidi Nucleici, CNR-IBPM, Roma, Italy (B.I.); Dipartimento di Scienze Chimiche, Università degli Studi di Roma \"Sapienza\", Roma, Italy (A.M.); Dipartimento di Scienze Farmaceutiche, Università degli Studi di Salerno, Fisciano (SA), Italy (S.C., G.S.); Istituto di Biologia Cellulare e Neurobiologia, Consiglio Nazionale delle Ricerche, Roma, Italy (S.M., A.F.); and Division of Cardiovascular Epigenetics, Department of Cardiology, Goethe University, Frankfurt am Main, Germany (C.G.). (literal)
- Titolo
- P300/CBP associated factor regulates nitroglycerin-dependent arterial relaxation by N(?)-lysine acetylation of contractile proteins (literal)
- Abstract
- Objective--To address the role of epigenetic enzymes in the process of arterial vasorelaxation and nitrate tolerance, in vitro and in vivo experiments were performed in the presence or absence of glyceryl trinitrate (GTN) or histone deacetylases/histone acetylases modulators.
Methods and Results--In vitro single GTN administration rapidly increased cGMP synthesis and protein N?-lysine acetylation in rat smooth muscle cells, including myosin light chain and smooth muscle actin. This phenomenon determined a decrease in myosin light chain phosphorylation and actomyosin formation. These effects were abolished by prolonged exposure to GTN and rescued by treatment with trichostatin A. In vivo, adult male rats were treated for 72 hours with subcutaneous injections of GTN alone or in combination with the histone deacetylases inhibitors trichostatin A, suberoylanilide hydroxamic acid, MS-27-275, or valproic acid. Ex vivo experiments performed on aortic rings showed that the effect of tolerance was reversed by all proacetylation drugs, including the p300/CREB binding protein-associated factor activator pentadecylidenemalonate 1b (SPV106). Any response to GTN was abolished by anacardic acid, a potent histone acetylases inhibitor.
Conclusion--This study establishes the following points: (1) GTN treatment increases histone acetylases activity; (2) GTN-activated p300/CREB binding protein-associated factor increases protein N?-lysine acetylation; (3) N?-lysine acetylation of contractile proteins influences GTN-dependent vascular response. Hence, combination of epigenetic drugs and nitroglycerin may be envisaged as a novel treatment strategy for coronary artery disease symptoms and other cardiovascular accidents of ischemic origin. (literal)
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