Role of O-GlcNacylation (O-GlcNAc) on the expression and function of classical estrogen receptor alpha (ERa66kDa) and splice variant of estrogen receptor alpha (ERa36kDa) in the common carotid artery of aging mice

• Grant number: 17/25116-2
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: July 01, 2018
• End date: February 28, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Cardiorenal Pharmacology
• Principal Investigator: Rita de Cassia Aleixo Tostes Passaglia
• Grantee: Tiago Januário da Costa
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 19/26374-0 - How does sex and estrogen impact the O-GlcNAc pathway? A proteomic approach, BE.EP.PD

Abstract

Estrogen receptors (ERa and ERb) mediate the beneficial effects of estrogen in the vasculature. However, estrogen produces different effects in the vasculature of aged, hypertensive and obese females, which is partially explained by changes in ER± and ER² expression. Estrogen receptors are ligand-inducible transcription factors regulated by serine (Ser) and threonine (Thr) phosphorylation. Ser and Thr can also be glycosylated and this process can influence ER phosphorylation in certain cases. The glycosylation with O-linked N-acetylglucosamine (O-GlcNAc) is a biological, highly dynamic and enzymatic process found on nuclear and cytoplasmic proteins. Augmented levels of O-GlcNAc-modified proteins have been associated to cardiovascular disease in male subjects. Accordingly, augmented O-GlcNAc levels increase endothelin-1 (ET-1)-induced vasoconstriction and the risk for cardiovascular disease in male rats. Cardiovascular diseases develop approximately 10 years later in women compared to men and are still the major cause of death in women over 65 years. The increased risk of cardiovascular diseases in postmenopausal women has been linked to a reduction of plasma estrogen levels. However, estrogen therapy effects on cardiovascular diseases have been questioned. In this project, we will test the hypothesis that O-GlcNAc inhibits the protective effects of estrogen in the common carotid artery, important to blood supply to the brain, by reducing the phosphorylation of ER±-dependent in aged female mice. Our study may shed light to new pharmacological treatments for cardiovascular disease for postmenopausal women. (AU)

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)

COSTA, TIAGO J.; POTJE, SIMONE R.; FRAGA-SILVA, THAIS F. C.; DA SILVA-NETO, JULIO A.; BARROS, PAULA R.; RODRIGUES, DANIEL; MACHADO, MIRELE R.; MARTINS, RONALDO B.; SANTOS-EICHLER, ROSANGELA A.; BENATTI, MAIRA N.; et al. itochondrial DNA and TLR9 activation contribute to SARS-CoV-2-induced endothelial cell damag. VASCULAR PHARMACOLOGY, v. 142, FEB 2022. (13/08216-2, 16/21239-0, 17/25116-2)

MARTUCCI, LUIZ FELIPE; EICHLER, ROSANGELA A. S.; SILVA, RENEE N. O.; COSTA, TIAGO J.; TOSTES, RITA C.; BUSATTO, GERALDO F.; SEELAENDER, MARILIA C. L.; DUARTE, ALBERTO J. S.; SOUZA, HERALDO P.; FERRO, EMER S.. Intracellular peptides in SARS-CoV-2-infected patients. ISCIENCE, v. 26, n. 9, p. 17-pg., 2023-09-15. (13/08216-2, 16/04000-3, 17/25116-2)

POTJE, SIMONE R.; COSTA, TIAGO J.; FRAGA-SILVA, THAIS F. C.; MARTINS, RONALDO B.; BENATTI, MAIRA N.; ALMADO, CARLOS E. L.; DE SA, KEYLA S. G.; BONATO, VANIA L. D.; ARRUDA, EURICO; LOUZADA-JUNIOR, PAULO; et al. Heparin prevents in vitro glycocalyx shedding induced by plasma from COVID-19 patients. Life Sciences, v. 276, JUL 1 2021. (17/25116-2, 16/21239-0, 13/08216-2, 20/05270-0)

COSTA, TIAGO J.; BARROS, PAULA R.; DUARTE, DIEGO A.; SILVA-NETO, JULIO A.; HOTT, SARA CRISTINA; SANTOS-SILVA, THAMYRIS; COSTA-NETO, CLAUDIO M.; V. GOMES, FELIPE; AKAMINE, ELIANA H.; MCCARTHY, CAMERON G.; et al. Carotid dysfunction in senescent female mice is mediated by increased a1A-adrenoceptor activity and COX-derived vasoconstrictor prostanoids. AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, v. 324, n. 4, p. 13-pg., 2023-04-01. (13/08216-2, 17/25116-2)