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Contribution of the transcription factor Nrf2 for the vascular alterations associated with arterial hypertension induced by aldosterone

Grant number: 18/05298-1
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): June 01, 2018
Effective date (End): December 31, 2020
Field of knowledge:Biological Sciences - Pharmacology - Cardiorenal Pharmacology
Principal researcher:Rita de Cassia Aleixo Tostes Passaglia
Grantee:Daniel Rodrigues
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
Associated scholarship(s):19/22303-1 - The role of Nrf2 and redox signaling in aldosterone-induced vascular dysfunction, BE.EP.IC

Abstract

Aldosterone (Aldo), synthesized mainly in the glomerular zone of the adrenal tissue, but also in extra-renal tissues such as the central nervous system and the cardiovascular system, is a mineralocorticoid (MR) receptor agonist. Aldo's main function is the regulation of the hydroelectrolytic balance, by increasing the reabsorption of the sodium ion (Na+), decreasing plasma concentrations of potassium (K+) and by activation of the renin-angiotensin system. In the cardiovascular system Aldo favors the generation of reactive oxygen species (ROS) via activation of the NAD(P)H oxidase enzyme. ROS contribute to vascular dysfunction by reducing the bioavailability of nitric oxide in endothelial cells and, consequently, increasing the contractile tone of the vascular smooth muscle cells. Various cell types developed adaptive programs to neutralize oxidative stress. The erythroid nuclear factor 2 related to factor 2 (Nrf2), for example, recruits the transcriptional machinery to promote expression of various antioxidant proteins. The transcriptional activity of Nrf2 is finely regulated by repressor proteins, including Keap-1 and the nuclear Bach-1, proteins that inhibit its activity. Considering that Aldo is a potent inducer of ROS and that Nrf2 is a redox-sensitive transcription factor that activates transcription of antioxidant genes, we hypothesized that Aldo negatively regulates the antioxidant system Nrf2, via increased expression of Keap-1 and Bach-1, favoring the accumulation of ROS and subsequent vascular dysfunction (AU)

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Scientific publications
(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)
RODRIGUES, DANIEL; COSTA, TIAGO J.; SILVA, JOSIANE F.; NETO, JOSE TELES DE OLIVEIRA; ALVES, JULIANO V.; FEDOCE, ALINE G.; COSTA, RAFAEL MENEZES; TOSTES, RITA C.. Aldosterone Negatively Regulates Nrf2 Activity: An Additional Mechanism Contributing to Oxidative Stress and Vascular Dysfunction by Aldosterone. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 22, n. 11, . (13/08216-2, 18/05298-1)

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