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Evaluation of post-translational modification mechanisms of endothelial Nitric Oxide Synthase (eNOS) associated with the nitric oxide bioavailability in Spontaneously Hypertensive Rats (SHR) in the end of pregnancy

Grant number: 15/09373-0
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): September 01, 2017
Effective date (End): April 30, 2019
Field of knowledge:Biological Sciences - Pharmacology
Principal Investigator:Cristina Antoniali Silva
Grantee:Jéssica Antonini Troiano
Host Institution: Faculdade de Odontologia (FOA). Universidade Estadual Paulista (UNESP). Campus de Araçatuba. Araçatuba , SP, Brazil


Previous studies from our laboratory suggest that pregnancy is a favorable physiological condition to reduced blood pressure, vascular reactivity to alpha1-adrenergic stimulation and to reestablishment of the endothelial function in Spontaneously Hypertensive Rats (SHR). In pregnant SHR, the increased production and bioavailability of NO, resulting from increased phosphorylation of the PI3K-Akt- eNOS pathway, reestablished endothelium-eNOS-dependent modulation on aortas reactivity to phenylephrine (PE). The objective of this study is to analyze possible alterations in post-translational modification mechanisms associated to increased eNOS activity in blood vessel of pregnant SHR. The glycosylation of eNOS by hexosamine pathway and protein-protein interactions associated to eNOS phosphorylation will be investigate in blood vessel of normotensive pregnant rats and pregnant SHR. Western Blot Assays will performed to analyze following proteins expression: O-GlcNAc transferase, O-GlcNAc, eNOS, p-eNOS, CAV-1, P-CAV-1, Hsp90, p-Hsp90, calmodulin (CaM) as well as their interactions by co-immunoprecipitation method. In functional studies, we will evaluate the participation of pos-translational mechanisms on vascular hiporeactivity to phenilefrine associated to pregnancy. We will evaluate the participation of OGA, by inhibition with PUGNAc (100 mmol/L) and Hsp90, by inhibition with Geldamycin (1 mmol/L) or radicicol (20 nmol/L). The results will be analyzed by ANOVA multivariance test, two-way, and the significative differences will be considered when p <0.05. (AU)

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
TROIANO, JESSICA A.; POTJE, SIMONE R.; GRATON, MURILO E.; SILVA, DANIELA S.; DA COSTA, RAFAEL M.; TOSTES, RITA C.; ANTONIALI, CRISTINA. Pregnancy decreases O-GlcNAc-modified proteins in systemic arteries of normotensive and spontaneously hypertensive rats. Life Sciences, v. 266, . (16/22180-9, 15/09373-0)
BARROSO, HELENA C.; GRATON, MURILO E.; POTJE, SIMONE R.; TROIANO, JESSICA A.; SILVA, LILIAN X.; NAKAMUNE, ANA CLAUDIA M. S.; ANTONIALI, CRISTINA. Data of Nebivolol on oxidative stress parameters in hypertensive patients. DATA IN BRIEF, v. 41, p. 11-pg., . (16/22180-9, 17/18436-0, 15/09373-0)
TROIANO, JESSICA ANTONINI; POTJE, SIMONE REGINA; GRATON, MURILO; SILVA, DANIELA DE SOUZA; COSTA, RAFAEL MENEZES; TOSTES, RITA DE CASSIA; ANTONIALI, CRISTINA. O-GlcNAcylation is decreased in aorta and mesenteric artery in normotensive and hypertensive pregnant rats. Free Radical Biology and Medicine, v. 128, p. 1-pg., . (16/22180-9, 15/09373-0)
TROIANO, JESSICA ANTONINI; GRATON, MURILO EDUARDO; POTJE, SIMONE REGINA; GONCALVES, EMILY THALIA; DE OLIVEIRA FONSECA ZANARDO, JESSICA LUIZA; BENEVIDES, PRISCILA SCARPIM; ANTONIALI, CRISTINA. Distinct Role of Endothelial Caveolae in Contraction and Relaxation Responses of Aortas from Pregnant Normotensive and hypertensive Rates. FASEB JOURNAL, v. 33, p. 2-pg., . (18/10635-7, 15/09373-0, 16/22180-9)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)

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