DENISE DE CASTRO FERNANDES
Projetos de Pesquisa
Unidades Organizacionais
LIM/19 - Laboratório de Histocompatibilidade e Imunidade Celular, Hospital das Clínicas, Faculdade de Medicina
36 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 36
- Time-Dependent Effects of Training on Cardiovascular Control in Spontaneously Hypertensive Rats: Role for Brain Oxidative Stress and Inflammation and Baroreflex Sensitivity(2014) MASSON, Gustavo S.; COSTA, Tassia S. R.; YSHII, Lidia; FERNANDES, Denise C.; SOARES, Pedro Paulo Silva; LAURINDO, Francisco R.; SCAVONE, Cristoforo; MICHELINI, Lisete C.Baroreflex dysfunction, oxidative stress and inflammation, important hallmarks of hypertension, are attenuated by exercise training. In this study, we investigated the relationships and time-course changes of cardiovascular parameters, pro-inflammatory cytokines and pro-oxidant profiles within the hypothalamic paraventricular nucleus of the spontaneously hypertensive rats (SHR). Basal values and variability of arterial pressure and heart rate and baroreflex sensitivity were measured in trained (T, low-intensity treadmill training) and sedentary (S) SHR at weeks 0, 1, 2, 4 and 8. Paraventricular nucleus was used to determine reactive oxygen species (dihydroethidium oxidation products, HPLC), NADPH oxidase subunits and pro-inflammatory cytokines expression (Real time PCR), p38 MAPK and ERK1/2 expression (Western blotting), NF-kappa B content (electrophoretic mobility shift assay) and cytokines immunofluorescence. SHR-S vs. WKY-S (Wistar Kyoto rats as time control) showed increased mean arterial pressure (172 +/- 3 mmHg), pressure variability and heart rate (358 +/- 7 b/min), decreased baroreflex sensitivity and heart rate variability, increased p47(phox) and reactive oxygen species production, elevated NF-kappa B activity and increased TNF-alpha and IL-6 expression within the paraventricular nucleus of hypothalamus. Two weeks of training reversed all hypothalamic changes, reduced ERK1/2 phosphorylation and normalized baroreflex sensitivity (4.04 +/- 0.31 vs. 2.31 +/- 0.19 b/min/mmHg in SHR-S). These responses were followed by increased vagal component of heart rate variability (1.9-fold) and resting bradycardia (-13%) at the 4th week, and, by reduced vasomotor component of pressure variability (-28%) and decreased mean arterial pressure (-7%) only at the 8th week of training. Our findings indicate that independent of the high pressure levels in SHR, training promptly restores baroreflex function by disrupting the positive feedback between high oxidative stress and increased pro-inflammatory cytokines secretion within the hypothalamic paraventricular nucleus. These early adaptive responses precede the occurrence of training-induced resting bradycardia and blood pressure fall.
conferenceObject Reflex modulation of vasomotor sympathetic and peripheral autonomic control on hypertension: Sequential effects of aerobic training(2020) MASSON, Gustavo Santos; FERNANDES, Denise; YSHII, Lidia; SOARES, Pedro Paulo; LAURINDO, Francisco R.; SCAVONE, Cristoforo; MICHELINIL, Lisete C.conferenceObject Beneficial effects of physical exercise on functional capacity and skeletal muscle oxidative stress in rats with aortic stenosis-induced heart failure(2016) GOMES, M. J.; MARTINEZ, P. F.; PAGAN, L. U.; LIMA, A. R. R.; DAMATTO, R. L.; CEZAR, M. D. M.; FERNANDES, A. A. H.; FERNANDES, D. C.; LAURINDO, F. R.; OKOSHI, K.; OKOSHI, M. P.- Nitroarachidonic Acid (NO(2)AA) Inhibits Protein Disulfide Isomerase (PDI) Through Reversible Covalent Adduct Formation with Critical Cysteine Residues(2016) GONZALEZ-PERILLI, Lucia; MASTROGIOVANNI, Mauricio; FERNANDES, Denise; RUBBO, Homero; LAURINDO, Francisco; TROSTCHANSKY, Andres
- PDIA1 overexpression activates acutely Nox1 NADPH oxidase in VSMC(2015) GONCALVES, Renata; ZANATA, Daniela; STRAUSS, Bryan; LAURINDO, Francisco Rafael; FERNANDES, Denise de Castro
- Conserved Gene Microsynteny Unveils Functional Interaction Between Protein Disulfide Isomerase and Rho Guanine-Dissociation Inhibitor Families(2017) MORETTI, Ana I. S.; PAVANELLI, Jessyca C.; NOLASCO, Patricia; LEISEGANG, Matthias S.; TANAKA, Leonardo Y.; FERNANDES, Carolina G.; WOSNIAK JR., Joao; KAJIHARA, Daniela; DIAS, Matheus H.; FERNANDES, Denise C.; JO, Hanjoong; Ngoc-Vinh Tran; EBERSBERGER, Ingo; BRANDES, Ralf P.; BONATTO, Diego; LAURINDO, Francisco R. M.Protein disulfide isomerases (PDIs) support endoplasmic reticulum redox protein folding and cell-surface thiol-redox control of thrombosis and vascular remodeling. The family prototype PDIA1 regulates NADPH oxidase signaling and cytoskeleton organization, however the related underlying mechanisms are unclear. Here we show that genes encoding human PDIA1 and its two paralogs PDIA8 and PDIA2 are each flanked by genes encoding Rho guanine-dissociation inhibitors (GDI), known regulators of RhoGTPases/cytoskeleton. Evolutionary histories of these three microsyntenic regions reveal their emergence by two successive duplication events of a primordial gene pair in the last common vertebrate ancestor. The arrangement, however, is substantially older, detectable in echinoderms, nematodes, and cnidarians. Thus, PDI/RhoGDI pairing in the same transcription orientation emerged early in animal evolution and has been largely maintained. PDI/RhoGDI pairs are embedded into conserved genomic regions displaying common cis-regulatory elements. Analysis of gene expression datasets supports evidence for PDI/RhoGDI coexpression in developmental/inflammatory contexts. PDIA1/RhoGDIa were co-induced in endothelial cells upon CRISP-R-promoted transcription activation of each pair component, and also in mouse arterial intima during flow-induced remodeling. We provide evidence for physical interaction between both proteins. These data support strong functional links between PDI and RhoGDI families, which likely maintained PDI/RhoGDI microsynteny along > 800-million years of evolution.
article 36 Citação(ões) na Scopus Tobacco Smoke Induces Ventricular Remodeling Associated with an Increase in NADPH Oxidase Activity(2011) RAFACHO, Bruna P. M.; AZEVEDO, Paula S.; POLEGATO, Bertha F.; FERNANDES, Ana A. H.; BERTOLINE, Maria A.; FERNANDES, Denise C.; CHIUSO-MINICUCCI, Fernanda; ROSCANI, Meliza G.; SANTOS, Priscila P. dos; MATSUBARA, Luiz S.; MATSUBARA, Beatriz B.; LAURINDO, Francisco R. M.; PAIVA, Sergio A. R.; ZORNOFF, Leonardo A. M.; MINICUCCI, Marcos F.Background: Recent studies have assessed the direct effects of smoking on cardiac remodeling and function. However, the mechanisms of these alterations remain unknown. The aim of this study was to investigate de role of cardiac NADPH oxidase and antioxidant enzyme system on ventricular remodeling induced by tobacco smoke. Methods: Male Wistar rats that weighed 200-230 g were divided into a control group (C) and an experimental group that was exposed to tobacco smoke for a period of two months (ETS). After the two-month exposure period, morphological, biochemical and functional analyses were performed. Results: The myocyte cross-sectional area and left ventricle end-diastolic dimension was increased 16.2% and 33.7%, respectively, in the ETS group. The interstitial collagen volume fraction was also higher in ETS group compared to the controls. In addition to these morphological changes, the ejection fraction and fractional shortening were decreased in the ETS group. Importantly, these alterations were related to augmented heart oxidative stress, which was characterized by an increase in NADPH oxidase activity, increased levels of lipid hydroperoxide and depletion of antioxidant enzymes (e.g., catalase, superoxide dismutase and glutathione peroxidase). In addition, cardiac levels of IFN-gamma, TNF-alpha and IL-10 were not different between the groups. Conclusion: Cardiac alterations that are induced by smoking are associated with increased NADPH oxidase activity, suggesting that this pathway plays a role in the ventricular remodeling induced by exposure to tobacco smoke.- Apocynin influence on oxidative stress and cardiac remodeling of spontaneously hypertensive rats with diabetes mellitus(2016) ROSA, C. M.; GIMENES, R.; CAMPOS, D. H. S.; GUIRADO, G. N.; GIMENES, C.; FERNANDES, A. A. H.; CICOGNA, A. C.; QUEIROZ, R. M.; FALCAO-PIRES, I.; MIRANDA-SILVA, D.; RODRIGUES, P.; LAURINDO, F. R.; FERNANDES, D. C.; CORREA, C. R.; OKOSHI, M. P.; OKOSHI, K.Purpose: Although increased oxidative stress is a major component of diabetic hypertensive cardiomyopathy, research into the effects of antioxidants on cardiac remodeling remains scarce. The actions of antioxidant apocynin include inhibiting reactive oxygen species (ROS) generation by nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and ROS scavenging. We evaluated the effects of apocynin on cardiac remodeling in spontaneously hypertensive rats (SHR) with diabetes mellitus (DM). Methods: Male SHR were divided into four groups: control (SHR, n = 16); SHR treated with apocynin (SHR-APO; 16 mg/kg/day, added to drinking water; n = 16); diabetic SHR (SHR-DM, n = 13); and SHR-DM treated with apocynin (SHR-DM-APO, n = 14), for eight weeks. DM was induced by streptozotocin (40 mg/kg, single dose). Statistical analyzes: ANOVA and Tukey or Mann-Whitney. Results: Echocardiogram in diabetic groups showed higher left ventricular and left atrium diameters indexed for body weight, and higher isovolumetric relaxation time than normoglycemic rats; systolic function did not differ between groups. Isolated papillary muscle showed impaired contractile and relaxation function in diabetic groups. Developed tension was lower in SHR-APO than SHR. Myocardial hydroxyproline concentration was higher in SHR-DM than SHR, interstitial collagen fraction was higher in SHR-DM-APO than SHR-APO, and type III collagen protein expression was lower in SHR-DM and SHR-DM-APO than their controls. Type I collagen and lysyl oxidase expression did not differ between groups. Apocynin did not change collagen tissue. Myocardial lipid hydroperoxide concentration was higher in SHR-DM than SHR and SHR-DM-APO. Glutathione peroxidase activity was lower and catalase higher in SHR-DM than SHR. Apocynin attenuated antioxidant enzyme activity changes in SHR-DM-APO. Advanced glycation end-products and NADPH oxidase activity did not differ between groups. Conclusion: Apocynin reduces oxidative stress independently of NADPH oxidase activity and does not change ventricular or myocardial function in spontaneously hypertensive rats with diabetes mellitus. The apocynin-induced myocardial functional impairment in SHR shows that apocynin actions need to be clarified during sustained chronic pressure overload.
- Antioxidant Activity of Uruguayan Propolis. In Vitro and Cellular Assays(2011) SILVA, Veronica; GENTA, Gonzalo; MOELLER, Matias N.; MASNER, Martin; THOMSON, Leonor; ROMERO, Natalia; RADI, Rafael; FERNANDES, Denise C.; LAURINDO, Francisco R. M.; HEINZEN, Horacio; FIERRO, Walter; DENICOLA, AnaThe antioxidant capacity of propolis from the southern region of Uruguay was evaluated using in vitro as well as cellular assays. Free radical scavenging capacity was assessed by ORAC, obtaining values significantly higher than those of other natural products (8000 mu mol Trolox equiv/g propolis). ORAC values correlated well with total polyphenol content (determined by Folin-Ciocalteu method) and UV absorption. Total polyphenol content (150 mg gallic acid equiv/g propolis) and flavonoids (45 mg quercetin equiv/g propolis) were similar to values reported for southern Brazilian (group 3) and Argentinean propolis. Flavonoid composition determined by RP-HPLC indicates a strong poplar-tree origin. Samples high in polyphenols efficiently inhibit low-density lipoprotein lipoperoxidation and tyrosine nitration. In addition, Uruguayan propolis was found to induce the expression of endothelial nitric oxide synthase and inhibit endothelial NADPH oxidase, suggesting a potential cardiovascular benefit by increasing nitric oxide bioavailability in the endothelium.
- Endothelium-Dependent Vasodilation: Nitric Oxide and Other Mediators(2018) LAURINDO, F. R. M.; LIBERMAN, M.; FERNANDES, D. C.; LEITE, P. F.Vasodilation is the archetypal function of the endothelial cell and the discovery of paracrine-dependent vasorelaxation by endothelium-derived production of the gaseous mediator nitric oxide (NO) was revolutionary. NO mediates its regulatory vasorelaxing effects through guanilyl cyclase activation. Also, thiol S-nitrosation by NO is increasingly evident as an effector mechanism. Another important NO-related chemistry is its reaction with superoxide radicals, yielding peroxynitrite and related oxidant and nitrating species associated with toxic effects. Nitrogen oxides are storage forms of NO which can exert vasodilation in the presence of hemeproteins. NO generation is mediated by NO synthase enzymes (endothelial, neuronal, and inducible isoforms), which depict complex regulation dependent on cofactors. The absence of such cofactors can uncouple NO generation from electron transfer, generating superoxide. The endothelium additional promotes vasodilation, mainly of small resistance arteries, through endothelium-derived hyperpolarizing factor(s) such as hydrogen peroxide, epoximetabolites of arachidonic acid, and gap junctions. Hydrogen sulfide is a novel gaseous endothelium-derived vasodilator. Together, these mechanisms compose an integrative platform providing an endothelium-associated dilator tone. © 2018 Elsevier Inc. All rights reserved.