FRANCISCO RAFAEL MARTINS LAURINDO
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
62 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 62
- Transit of H2O2 across the endoplasmic reticulum membrane is not sluggish(2016) APPENZELLER-HERZOG, Christian; BANHEGYI, Gabor; BOGESKI, Ivan; DAVIES, Kelvin J. A.; DELAUNAY-MOISAN, Agnes; FORMAN, Henry Jay; GOERLACH, Agnes; KIETZMANN, Thomas; LAURINDO, Francisco; MARGITTAI, Eva; MEYER, Andreas J.; RIEMER, Jan; RUTZLER, Michael; SIMMEN, Thomas; SITIA, Roberto; TOLEDANO, Michel B.; TOUW, Ivo P.Cellular metabolism provides various sources of hydrogen peroxide (H2O2) in different organelles and compartments. The suitability of H2O2 as an intracellular signaling molecule therefore also depends on its ability to pass cellular membranes. The propensity of the membranous boundary of the endoplasmic reticulum (ER) to let pass H2O2 has been discussed controversially. In this essay, we challenge the recent proposal that the ER membrane constitutes a simple barrier for H2O2 diffusion and support earlier data showing that (i) ample H2O2 permeability of the ER membrane is a prerequisite for signal transduction, (ii) aquaporin channels are crucially involved in the facilitation of H2O2 permeation, and (iii) a proper experimental framework not prone to artifacts is necessary to further unravel the role of H2O2 permeation in signal transduction and organelle biology.
- Golgi-independent routes support protein disulfide isomerase externalization in vascular smooth muscle cells(2017) ARAUJO, Thais L. S.; FERNANDES, Carolina G.; LAURINDO, Francisco R. M.Extracellular pools of intracellular molecular chaperones are increasingly evident. The peri/epicellular(pec) pool of the endoplasmic reticulum redox chaperone protein disulfide isomerase-A1(PDI) is involved in thrombosis and vascular remodeling, while PDI externalization routes remain elusive. In endothelial cells, vesicular-type PDI secretion involves classical and unconventional pathways, while in platelets PDI exocytosis involves actin cytoskeleton. However, little is known about pecPDI in vascular smooth muscle cells(VSMC). Here, we showed that VSMC display a robust cell-surface(cs) PDI pool, which binds to cs independently of electrostatic forces. However, contrarily to other cells, soluble secreted PDI pool was undetectable in VSMC. Calcium ionophore A23187 and TNF alpha enhanced VSMC csPDI. Furthermore, VSMC PDI externalization occurred via Golgi-bypass unconventional route, which was independent of cytoskeleton or lysosomes. Secreted PDI was absent in ex vivo wild-type mice aortas but markedly enhanced in PDI-overexpressing mice. Such characterization of VSMC pecPDI reinforces cell-type and context specific routes of PDI externalization.
- Unfolded Protein Response: Cause or Consequence of Lipid and Lipoprotein Metabolism Disturbances?(2019) PINTO, Bruno Araujo Serra; FRANCA, Lucas Martins; LAURINDO, Francisco Rafael Martins; PAES, Antonio Marcus de AndradeThe liver plays a capital role in the control of whole body energy homeostasis through the metabolization of dietary carbohydrates and lipids. However, under excess macronutrient uptake, those pathways overcharge nucleus-to-endoplasmic reticulum (ER) traffic pathways, leading to luminal overload of unfolded proteins which activates a series of adaptive signaling pathways known as unfolded protein response (UPR). The UPR is a central network mechanism for cellular stress adaptation, however far from a global nonspecific all-or-nothing response. Such a complex signaling network is able to display considerable specificity of responses, with activation of specific signaling branches trimmed for distinct types of stimuli. This makes the UPR a fundamental mechanism underlying metabolic processes and diseases, especially those related to lipid and carbohydrate metabolism. Thus, for a better understanding of the role of UPR on the physiopathology of lipid metabolism disorders, the concepts discussed along this chapter will demonstrate how several metabolic derangements activate UPR components and, in turn, how UPR triggers several metabolic adaptations through its component signaling proteins. This dual role of UPR on lipid metabolism will certainly foment the pursuit of an answer for the question: is UPR cause or consequence of lipid and lipoprotein metabolism disturbances?
- 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
- Protein disulfide isomerases: Redox connections in and out of the endoplasmic reticulum(2017) MORETTI, Ana Iochabel Soares; LAURINDO, Francisco Rafael MartinsProtein disulfide isomerases are thiol oxidoreductase chaperones from thioredoxin superfamily. As redox folding catalysts from the endoplasmic reticulum (ER), their roles in ER-related redox homeostasis and signaling are well-studied. PDIA1 exerts thiol oxidation/reduction and isomerization, plus chaperone effects. Also, substantial evidence indicates that PDIs regulate thiol-disulfide switches in other cell locations such as cell surface and possibly cytosol. Subcellular PDI translocation routes remain unclear and seem Golgi-independent. The list of signaling and structural proteins reportedly regulated by PDIs keeps growing, via thiol switches involving oxidation, reduction and isomerization, S-(de)nytrosylation, (de) glutathyonylation and protein oligomerization. PDIA1 is required for agonist-triggered Nox NADPH oxidase activation and cell migration in vascular cells and macrophages, while PDIA1-dependent cytoskeletal regulation appears a converging pathway. Extracellularly, PDIs crucially regulate thiol redox signaling of thrombosis/platelet activation, e.g., integrins, and PDIA1 supports expansive caliber remodeling during injury repair via matrix/cytoskeletal organization. Some proteins display regulatory PDI-like motifs. PDI effects are orchestrated by expression levels or post-translational modifications. PDI is redox-sensitive, although probably not a mass-effect redox sensor due to kinetic constraints. Rather, the ""all-in-one"" organization of its peculiar redox/chaperone properties likely provide PDIs with precision and versatility in redox signaling, making them promising therapeutic targets. (C) 2016 Published by Elsevier Inc.
conferenceObject Polyphenol-Rich Extract of Syzygium cumini Leaf Reduces Non-alcoholic Fatty Liver Disease in MSG-obese Mice by a Joint Action on Insulin Resistance and Endoplasmic Reticulum Stress(2017) FRANCA, Lucas Matins; SANTOS, Pamela Costa dos; FLISTER, Karla Frida Torres; VALE, Caroline Castro; SANCHES, Jonas Rodrigues; BENEVIDES, Renata Ohana Alves; RIBEIRO, Nathalee Liberal Xavier; LAURINDO, Francisco Rafael Martins; PAES, Antonio Marcus de Andrade- EXTRACELLULAR VESICLES AS PARACRINE REDOX REGULATORS OF THROMBOSIS AND HAEMOSTASIS(2023) GASPAR, Renato S.; LAURINDO, Francisco R. M.
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 MartinsconferenceObject Sustained Exposure to High-Sucrose Diet Triggers Endoplasmic Reticulum Stress in Hippocampus and Anticipates Cognitive and Motor Impairments in Adults Rats(2017) PINTO, Bruno Araujo Serra; MELO, Thamys Marinho; FLISTER, Karla Frida Torres; FRANCA, Lucas Martins; KAJIHARA, Daniela; MOREIRA, Vanessa Ribeiro; PEREIRA, Silma Regina Ferreira; LAURINDO, Francisco Rafael Martins; PAES, Antonio Marcus De Andrade- PDIA1 overexpression activates acutely Nox1 NADPH oxidase in VSMC(2015) GONCALVES, Renata; ZANATA, Daniela; STRAUSS, Bryan; LAURINDO, Francisco Rafael; FERNANDES, Denise de Castro