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Grant number: 18/06998-7
Support Opportunities:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): September 03, 2018
Effective date (End): September 02, 2019
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Principal Investigator:Sandra Lia do Amaral Cardoso
Grantee:Naiara Araújo Herrera
Supervisor: Jeannette Vasquez Vivar
Host Institution: Faculdade de Ciências (FC). Universidade Estadual Paulista (UNESP). Campus de Bauru. Bauru , SP, Brazil
Research place: Medical College of Wisconsin (MCW), United States  
Associated to the scholarship:16/12532-5 - Exercise training effects on SHR treated with dexamethasone: role of miRNAs, BP.DR


Dexamethasone (DEX) is used as anti-inflammatory and immunosuppressant drug. DEX treatment side-effects are several including muscle weakness, hypertension and microvascular rarefaction, which is attributed to an imbalance in angiogenesis and apoptotic signaling. DEX alters mitochondrial function in muscle cells but nothing is known of DEX effects in endothelial cells that could explain induced rarefaction. Physical training improves mitochondrial function and biogenesis by increasing Sirtuin 1 (Sirt-1) activity and nicotinamide adenine dinucleotide (NAD+) production. We have shown that physical training ameliorates vascular dysfunction and inhibits rarefaction in DEX treatments by mechanisms not fully understood. Thus, the overall goal of this project is to investigate if exercise training prevents DEX-induced vascular rarefaction by improving mitochondrial function. We will establish the effects of DEX in metabolic biomarkers using sedentary and trained muscles and interrogate specific changes in mitochondrial function in cells. Specifically, we will (1) establish the effects of DEX on NAD+, redox changes and cell apoptosis ; (2) establish the effects of DEX on bioenergetics using extra cellular flux bioenergetics analysis. The changes in mitochondrial biogenesis and mitophagy will be performed by confocal fluorescence, qPCR, and western blots; and (3) verify whether mitochondrial-targeted antioxidants (mito-Q and mitoCP) improve mitochondrial and cellular bioenergetics in DEX-treatment. As a result of this project, we will better understand the biochemical mechanisms involved in DEX-induced rarefaction and conceivably identify additional measures to control its vascular effects.

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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)
HERRERA, NAIARA ARAUJO; DE SOUZA, FRANCINE DUCHATSCH RIBEIRO; TARDELLI, LIDIELI PAZIN; DIONISIO, THIAGO JOSE; DOS SANTOS, CARLOS FERREIRA; VASQUEZ-VIVAR, JEANNETTE; DO AMARAL, SANDRA PIA. Exercise Training-MicroRNA-126 Upregulation is Associated with Prevention of Dexamethasone-Mediated Microvascular Rarefaction. FASEB JOURNAL, v. 33, p. 2-pg., . (18/06998-7)
HERRERA, NAIARA A.; DUCHATSCH, FRANCINE; TARDELLI, LIDIELI P.; DIONISIO, THIAGO J.; SHINOHARA, ANDRE L.; SANTOS, CARLOS F.; AMARAL, SANDRA LIA. MicroRNA-126 upregulation, induced by training, plays a role in controlling microcirculation in dexamethasone treated rats. Molecular and Cellular Endocrinology, v. 505, . (18/06998-7, 17/14405-3, 16/12532-5, 17/00509-1, 15/03965-2)
HERRERA, NAIARA A.; DUCHATSCH, FRANCINE; TARDELLI, LIDIELI P.; DIONISIO, THIAGO J.; SANTOS, CARLOS F.; AMARAL, SANDRA L.. Dexamethasone Does Not Inhibit Treadmill Training-Induced Angiogenesis in Myocardium: Role of MicroRNA-126 Pathway. Journal of Cardiovascular Pharmacology, v. 76, n. 6, p. 708-714, . (18/06998-7, 17/00509-1, 16/12532-5, 17/14405-3, 15/03965-2)
HERRERA, NAIARA ARAUJO; DUCHATSCH, FRANCINE; KAHLKE, ALLISON; AMARAL, SANDRA LIA; VASQUEZ-VIVAR, JEANNETTE. In vivo vascular rarefaction and hypertension induced by dexamethasone are related to phosphatase PTP1B activation not endothelial metabolic changes. Free Radical Biology and Medicine, v. 152, p. 689-696, . (18/06998-7, 16/12532-5, 17/00509-1, 17/14405-3)

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