LEONARDO YUJI TANAKA
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Coração, Hospital das Clínicas, Faculdade de Medicina
LIM/64, Hospital das Clínicas, Faculdade de Medicina - Líder
LIM/64, Hospital das Clínicas, Faculdade de Medicina - Líder
28 resultados
Resultados de Busca
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conferenceObject Early exposure to high-sucrose diet triggers hippocampal endoplasmic reticulum-stress in young rats(2016) PAES, Antonio Marcus de Andrade; PINTO, Bruno Araujo Serra; MELO, Thamys Marinho; FLISTER, Karla Frida Torres; FRANCA, Lucas Martins; TANAKA, Leonardo Yudi; LAURINDO, Francisco Rafael Martins- Red wine and equivalent oral pharmacological doses of resveratrol delay vascular aging but do not extend life span in rats(2012) LUZ, Protasio L. da; TANAKA, Leonardo; BRUM, Patricia Chakur; DOURADO, Paulo Magno Martins; FAVARATO, Desiderio; KRIEGER, Jose Eduardo; LAURINDO, Francisco Rafael M.Objective: To investigate, in male Wistar rats, the effects of long-term moderate red wine (RW) consumption (equivalent to similar to 0.15 mg% resveratrol RS), or RS in low (L, 0.15 mg%) or high (H, 400 mg%) doses in chow. Background: Both RW and RS exhibit cardioprotection. RS extends lifespan in obese rats. It is unclear whether RW consumption or low-dose RS delay vascular aging and prolong life span in the absence of overt risk factors. Methods: Endpoints were aerobic performance, exercise capacity, aging biomarkers (p53,p16,p21, telomere length and telomerase activity in aortic homogenates), vascular reactivity. Data were compared with controls (C) given regular chow. Results: Expressions of p53 decreased similar to 50% similar to with RW and LRS (p < 0.05 vs. C), p16 by similar to 29% with RW (p < 0.05 vs. C) and p21 was unaltered. RW and LRS increased telomere length >6.5-fold vs. C, and telomerase activity increased with LRS and HRS. All treatments increased aerobic capacity (C 32.5 +/- 1.2, RW 38.7 + 1.7, LRS 38.5 + 1.6, HRS 38.3 + 1.8 mlO2 min(-1) kg(-1)), and RW or LRS also improved time of exercise tolerance vs. C (p < 0.05). Endothelium-dependent relaxation improved with all treatments vs. C. Life span, however, was unaltered with each treatment vs. C = 673 +/- 30 days, p = NS. Conclusions: RW and LRS can preserve vascular function indexes in normal rats, although not extending life span. These effects were translated into better aerobic performance and exercise capacity.
- 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.
- ATRX-DAXX Complex Expression Levels and Telomere Length in Normal Young and Elder Autopsy Human Brains(2019) CAVALCANTE, Stella G.; SILVA, Clarisse P. N.; SOLA, Paula R.; TANAKA, Leonardo Y.; OBA-SHINJO, Sueli M.; MARIE, Suely K. N.The chromatin-remodeling complex ATRX/DAXX is one of the major epigenetic factors that controls heterochromatin maintenance due to its role in histone deposition. ATRX is involved in nucleosome configuration and maintenance of higher order chromatin structure, and DAXX is a specific histone chaperone for H3.3 deposition. Dysfunctions in this complex have been associated with telomere shortening, which influences cell senescence. However, data about this complex in brain tissue related to aging are still scarce. Therefore, in the present study, we analyzed ATRX and DAXX expressions in autopsied human brain specimens and the telomere length. A significant decrease in gene and protein expressions was observed in the brain tissues from the elderly compared with those from the young, which were related to short telomeres. These findings may motivate further functional analysis to confirm the ATRX-DAXX complex involvement in telomere maintenance and brain aging.
conferenceObject Peri/epicellular protein disulfide isomerase PDI acts as an organizer of cytoskeletal mechanoadaptation in vascular smooth muscle cells(2018) TANAKA, Leonardo Yuji; ARAUJO, Thais Larissa; RODRIGUEZ, Andres Ignacio; FERRAZ, Mariana Sacrini Ayres; PELEGATI, Vitor Bianchin; SANTOS, Aline Mara; CESAR, Carlos Lens; ALENCAR, Adriano Mesquita; LAURINDO, Francisco Rafael Martins- Peri/epicellular Protein Disulfide Isomerase Reshapes Vascular Architecture to Counteracts Constrictive Remodeling(2014) TANAKA, Leonardo Yuji; ARAUJO, Haniel Alves; HIRONAKA, Gustavo Ken; ARAUJO, Thais Larissa; RODRIGUEZ, Andres Ignacio; CASAGRANDE, Annelise Silva; TAKIMURA, Celso Kiyoshi; LAURINDO, Francisco Rafael
- Hyperbaric oxygenation improves redox control and reduces mortality in the acute phase of myocardial infarction in a rat model(2020) OLIVEIRA, Mario S.; TANAKA, Leonardo Y.; ANTONIO, Ednei L.; I, Laura Brandizzi; SERRA, Andrey J.; SANTOS, Leonardo Dos; KRIEGER, Jose E.; LAURINDO, Francisco R. M.; TUCCI, Paulo J. F.Among the mechanisms of action of hyperbaric oxygenation (HBO), the chance of reducing injury by interfering with the mechanisms of redox homeostasis in the heart leads to the possibility of extending the period of viability of the myocardium at risk. This would benefit late interventions for reperfusion to the ischemic area. The objective of the present study was to investigate the changes in the redox system associated with HBO therapy maintained during the first hour after coronary occlusion in an acute myocardial infarction (MI) rat model. Surviving male rats (n=105) were randomly assigned to one of three groups: Sham (SH=26), myocardial infarction (MI=45) and infarction+hyperbaric therapy (HBO=34, 1 h at 2.5 atm). After 90 min of coronary occlusion, a sample of the heart was collected for western blot analysis of total protein levels of superoxide dismutase, catalase, peroxiredoxin and 3-nitrotyrosine. Glutathione was measured by enzyme-linked immunosorbent assay (ELISA). The detection of the superoxide radical anion was carried out by oxidation of dihydroethidium analyzed with confocal microscopy. The mortality rate of the MI group was significantly higher than that of the HBO group. No difference was noted in the myocardial infarction size. The oxidized/reduced glutathione ratio and peroxiredoxin were significantly higher in the SH and MI when compared to the HBO group. Superoxide dismutase enzymes and catalase were significantly higher in the HBO group compared to the MI and SH groups. 3-Nitrotyrosine and the superoxide radical were significantly lower in the HBO group compared to these in the MI and SH groups. These data demonstrated that hyperbaric oxygenation therapy decreased mortality by improving redox control in the hearts of rats in the acute phase of myocardial infarction.
conferenceObject Swimming training improves arterial vasomotor function in spontaneously hypertensive rats: role of reactive oxygen species and nitrogen(2014) JORDAO, C. P.; FERNANDES, T.; TANAKA, L.; OLIVEIRA, L. G.; BECHARA, L. G.; OLIVIERA, E. M.; RAMIRES, P. R.- Peri/Epicellular Protein Disulfide Isomerase Sustains Vascular Lumen Caliber Through an Anticonstrictive Remodeling Effect(2016) TANAKA, Leonardo Y.; ARAUJO, Haniel A.; HIRONAKA, Gustavo K.; ARAUJO, Thais L. S.; TAKIMURA, Celso K.; RODRIGUEZ, Andres I.; CASAGRANDE, Annelise S.; GUTIERREZ, Paulo S.; LEMOS-NETO, Pedro Alves; LAURINDO, Francisco R. M.Whole-vessel remodeling critically determines lumen caliber in vascular (patho)physiology, and it is reportedly redox-dependent. We hypothesized that the cell-surface pool of the endoplasmic reticulum redox chaperone protein disulfide isomerase-A1 (peri/epicellular=pecPDI), which is known to support thrombosis, also regulates disease-associated vascular architecture. In human coronary atheromas, PDI expression inversely correlated with constrictive remodeling and plaque stability. In a rabbit iliac artery overdistension model, there was unusually high PDI upregulation (approximate to 25-fold versus basal, 14 days postinjury), involving both intracellular and pecPDI. PecPDI neutralization with distinct anti-PDI antibodies did not enhance endoplasmic reticulum stress or apoptosis. In vivo pecPDI neutralization with PDI antibody-containing perivascular gel from days 12 to 14 post injury promoted 25% decrease in the maximally dilated arteriographic vascular caliber. There was corresponding whole-vessel circumference loss using optical coherence tomography without change in neointima, which indicates constrictive remodeling. This was accompanied by decreased hydrogen peroxide generation. Constrictive remodeling was corroborated by marked changes in collagen organization, that is, switching from circumferential to radial fiber orientation and to a more rigid fiber type. The cytoskeleton architecture was also disrupted; there was a loss of stress fiber coherent organization and a switch from thin to medium thickness actin fibers, all leading to impaired viscoelastic ductility. Total and PDI-associated expressions of 1-integrin, and levels of reduced cell-surface 1-integrin, were diminished after PDI antibody treatment, implicating 1-integrin as a likely pecPDI target during vessel repair. Indeed, focal adhesion kinase phosphorylation, a downstream 1-integrin effector, was decreased by PDI antibody. Thus, the upregulated pecPDI pool tunes matrix/cytoskeleton reshaping to counteract inward remodeling in vascular pathophysiology.
- Evidence for a protective role of Protein Disulfide Isomerase-A1 against aortic dissection(2023) PORTO, Fernando Garcez; TANAKA, Leonardo Yuji; BESSA, Tiphany Coralie de; OLIVEIRA, Percillia Victoria Santos; SOUZA, Julia Martins Felipe de; KAJIHARA, Daniela; FERNANDES, Carolina Goncalves; SANTOS, Patricia Nolasco; LAURINDO, Francisco Rafael MartinsBackground and aims: Redox signaling is involved in the pathophysiology of aortic aneurysm/dissection. Protein Disulfide Isomerases and its prototype PDIA1 are thiol redox chaperones mainly from endoplasmic reticulum (ER), while PDIA1 cell surface pool redox-regulates thrombosis, cytoskeleton remodeling and integrin activation, which are mechanisms involved in aortic disease. Here we investigate the roles of PDIA1 in aortic dissection. Methods: Initially, we assessed the outcome of aortic aneurysm/dissection in transgenic PDIA1-overexpressing FVB mice using a model of 28-day exposure to lysyl oxidase inhibitor BAPN plus angiotensin-II infusion. In a second protocol, we assessed the effects of PDIA1 inhibitor isoquercetin (IQ) against aortic dissection in C57BL/6 mice exposed to BAPN for 28 days. Results: Transgenic PDIA1 overexpression associated with ca. 50% (p = 0.022) decrease (vs.wild-type) in mor-tality due to abdominal aortic rupture and protected against elastic fiber breaks in thoracic aorta. Conversely, exposure of mice to IQ increased thoracic aorta dissection-related mortality rates, from ca. 18%-50% within 28-days (p = 0.019); elastic fiber disruption and collagen deposition were also enhanced. The structurally-related compound diosmetin, which does not inhibit PDI, had negligible effects. In parallel, stretch-tension curves indicated that IQ amplified a ductile-type of biomechanical failure vs. control or BAPN-exposed mice aortas. IQ-induced effects seemed unassociated with nonspecific antioxidant effects or ER stress. In both models, echo-cardiographic analysis of surviving mice suggested that aortic rupture was dissociated from progressive dilatation. Conclusions: Our data indicate a protective role of PDIA1 against aortic dissection/rupture and potentially un-covers a novel integrative mechanism coupling redox and biomechanical homeostasis in vascular remodeling.
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