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
5 resultados
Resultados de Busca
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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
- 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.
- Effects of static magnetic field on vascular function and structure and their potential implications with redox regulation of actin cytoskeleton(2023) MASSUCATTO, Ricardo; BAHARAMI, Abasalt; GUTIERRE, Lucas; AIELLO, Clarice; LAURINDO, Francisco R.; TANAKA, Leonardo
- DNAJB12 and DNJB14 are non-redundant Hsp40 redox chaperones involved in endoplasmic reticulum protein reflux(2024) PURIFICACA, Aline Dias da; DEBBAS, Victor; TANAKA, Leonardo Yuji; GABRIEL, Gabriele Veronica de Mello; WOSNIAK JUNIOR, Joao; BESSA, Tiphany Coralie De; GARCIA-ROSA, Sheila; LAURINDO, Francisco Rafael Martins; OLIVEIRA, Percillia Victoria SantosBackground: The endoplasmic reticulum (ER) transmembrane chaperones DNAJB12(B12) and DNAJB14(B14) are cofactors that cooperate with cytosolic Heat Shock-70 protein (HSC70) facilitating folding/degradation of nascent membrane proteins and supporting the ER-membrane penetration of viral particles. Here, we assessed structural/functional features of B12/B14 with respect to their regulation by ER stress and their involvement in ER stress-mediated protein reflux.Methods: We investigated the effect of Unfolded Protein Response(UPR)-eliciting drugs on the expression/ regulation of B12-B14 and their roles in ER-to-cytosol translocation of Protein Disulfide Isomerase-A1(PDI).Results: We show that B12 and B14 are similar but do not seem redundant. They share predicted structural features and show high homology of their cytosolic J-domains, while their ER-lumen DUF1977 domains are quite dissimilar. Interactome analysis suggested that B12/B14 associate with different biological processes. UPR activation did not significantly impact on B12 gene expression, while B14 transcripts were up-regulated. Meanwhile, B12 and B14 (33.4 kDa isoform) protein levels were degraded by the proteasome upon acute reductive challenge. Also, B12 degradation was impaired upon sulfenic-acid trapping by dimedone. We originally report that knockdown of B12/B14 and their cytosolic partner SGTA in ER-stressed cells significantly impaired the amount of the ER redox-chaperone PDI in a cytosolic-enriched fraction. Additionally, B12 but not B14 overexpression increased PDI relocalization in non-stressed cells.Conclusions and general significance: Our findings reveal that B12/B14 regulation involves thiol redox processes that may impact on their stability and possibly on physiological effects. Furthermore, we provide novel evidence that these proteins are involved in UPR-induced ER protein reflux.