Navegando por Palavras-chave "Lysosomes"
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- ItemAcesso aberto (Open Access)Avaliação da biodisponibilidade de metais em sedimentos acidificados através da infusão de CO2 empregando bivalves (Crassostrea casar)(Universidade Federal de São Paulo, 2017-11-29) Medeiros, Tierry Val de [UNIFESP]; Cesar, Augusto [UNIFESP]; http://lattes.cnpq.br/7526259441170335; Universidade Federal de São Paulo (UNIFESP)CO2 capture and storage activities are employed in oil exploration wells and their by-products through a CO2 injection system to reduce emissions and CO2 concentration in the atmosphere. The potential risks of CO2 leakage and ocean acidification scenarios were evaluated for their implications for mobility and bioavailability in sediments with different levels of metals by means of toxicity tests using oysters of the Crassostrea gasar species, where the stability of the lysosomal membrane and mortality. The results showed that there was mobility of metals in the sediments for Cr and Ni metals only with reference sediments. The organisms exerted a metal detoxification behavior in all pH treatments. The stability of the lysosomal membrane was significantly compromised at pH 7 and 6.5 with the reference sediments. The low occurrence of mortality (14.28% only at pH 6.5 with enriched sediments), together with the biological responses, show the adaptation of these organisms to acidification scenarios. Oysters were considered a useful bioindicator for studies in acidification scenarios.
- ItemAcesso aberto (Open Access)Avaliação da relação entre ritmos biológicos e fisiologia dos lisossomos e sua participação em modelo de doença lisossômica(Universidade Federal de São Paulo (UNIFESP), 2016-03-31) Oliveira, Ana Carolina Barris de [UNIFESP]; D'Almeida, Vania [UNIFESP]; http://lattes.cnpq.br/7220411418339421; http://lattes.cnpq.br/5870528224268731; Universidade Federal de São Paulo (UNIFESP)The clock system is responsible for the orchestration observed in several physiological, cellular and molecular processes. This regulation is controlled by a molecular machinery that allows the ideal synchronization of each tissue to the organism and this control presents plasticity that ensures the adaptation of the system to environmental changes. Lysosomes, organelles responsible for cellular digestion, present circadian activities and the role of the clock system is being explored in Lysosomal Storage Diseases, in which oxidative stress has a participation in their pathophysiologies and is regulated by the clock system. Despite these information, the relation between lysosomes and clock system in poorly understood. Thus, the aim of this work was to evaluate consequences of lysosomal malfunction, induced by drug or genetic disorder, in clock system and redox state. Rat fibroblasts with the gene Bmal1 conjugated to luciferase were treated with lysosomal inhibitors at the peak and trough of Bmal1 expression for Bmal1 expression and superoxide dismutase (SOD1) analysis; rat cardiomyocytes were treated at the peak of expression of Bmal1 for clock genes expression and autophagy-related proteins analysis and; control individuals and Fabry Disease (FD) patients? fibroblasts were used for clock genes and antioxidant enzymes genes expression evaluation, SOD1 and LAMP-2 protein expression and verify if the GLA gene, mutated in FD, and ?-galactosidase A enzyme (?-gal A), deficient if FD, present circadian oscillation. Results obtained indicated that the lysosomal inhibition by drugs promotes phase advance or delay and period alterations in Bmal1 expression, depending on the moment of treatment ? peak or trough of Bmal1 expression; besides acute modifications in Bmal1 and Per1, clock genes, and, phosphorylated-AMPK and LC-3 expression, proteins involved in autophagy. FD patients? fibroblasts presented altered expression of clock genes, especially from the positive arm of regulation (BMAL1 and CLOCK); GLA gene presented circadian oscillation and ?-gal A seemed to be influenced by the clock system. Redox state regulation was altered by lysosomal inhibition by drugs, in FD patients? fibroblasts the antioxidant enzymes genes and SOD1 did not present compromised clock system regulation but the protein LAMP-2 had alterations of its rhythmicity in FD patients? cells. Based on all these analysis, we suggest that lysosomal inhibition, acute or chronic, promotes alterations in the molecular regulation of the clock system likely related to the increase of cytosolic calcium. Therefore, we concluded that lysosomes have a role in the regulation of clock system and redox state, and hypothesize that this may happen through calcium mobilization from the interior of these organelles to the cytosol.
- ItemSomente MetadadadosBiphosphinic palladacycle complex mediates lysosomal-membrane permeabilization and cell death in K562 leukaemia cells(Elsevier B.V., 2006-08-07) Barbosa, Christiano Marcello Vaz [UNIFESP]; Oliveira, Carlos Rocha [UNIFESP]; Nascimento, Fábio Dupart [UNIFESP]; Smith, Mickaela C. M.; Fausto, Damela M.; Soufen, Marco Antônio; Sena, Eliana; Araújo, Ronaldo de Carvalho [UNIFESP]; Tersariol, Ivarne Luis dos Santos [UNIFESP]; Bincoletto, Claudia [UNIFESP]; Caires, Antonio Carlos Favero; UMC; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP); Universidade Estadual de Campinas (UNICAMP)The cell death mechanism of cytotoxicity induced by the Biphosphinic Palladacycle Complex (BPC) was studied using a K562 leukaemia cell line. the IC50 values obtained for K562 cells post-72 h of BPC were less than 5.0 mu M by using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) and trypan blue assays. Using the Acridine Orange vital staining combining fluorescence microscopy it was observed that the complex triggers apoptosis in K562 cells, inducing DNA fragmentation, as analysed through electrophoresis. Lysosomal-membrane permeabilization was also observed in K562 cells post-5 h of BPC, which suggests intralysossomal accumulation by proton-trapping, since its pK(a) value ranged from 5.1 to 6.5. Caspase-3, and -6 activity induced by BPC in K562 cells was prevented by the cathepsin-B inhibitor [N-(L-3-transpropylcarbamoyl-oxirane-2-carbonyl)-L-isoleucyl-L-proline] (CA074). These events occurred in the presence of endogenous bcl-2 and bax expression. Acute toxicological studies demonstrated that BPC produces no lesions for liver and kidney fourteen-days after drug administration (100 mg/kg - i.p.). White and red blood cells of BPC-treated mice presented normal morphological characteristics. Taken together, these data suggest a novel lysosomal pathway for BPC-induced apoptosis, in which lysosomes are the primary target and cathepsin B acts as death mediator. (c) 2006 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosEstudo comparativo dos lisossomos no carcinoma ductal infiltrativo da mama, consoante o estado menopausal, receptores hormonais e características histopatológicas(Universidade Federal de São Paulo (UNIFESP), 1992) Girão, Manoel João Batista Castello [UNIFESP]; Baracat, Edmund Chada [UNIFESP]
- ItemSomente MetadadadosLysosomal exocytosis: An important event during invasion of lamp deficient cells by extracellular amastigotes of Trypanosoma cruzi(Elsevier B.V., 2009-06-26) Gaspar, Emanuelle Baldo [UNIFESP]; Mortara, Renato Arruda [UNIFESP]; Andrade, Luciana O.; Silva, Claudio Vieira da [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade Federal de Uberlândia (UFU); Dept MorfolTrypanosoma cruzi is an obligate intracellular organism in vertebrate hosts. Lysosomes are involved in parasite invasion. LAMP-1 and LAMP-2 are the most abundant glycoproteins of the lysosomal membrane. This Study is the first report on the invasion of T. cruzi extracellular amastigotes (EA) in single LAMP-1 or LAMP-2 knockouts, respectively, or in two independent LAMP-1/2 double-knockout cell lines. When compared to their respective wild type clones, the EA show higher infectivity in LAMP-2 knockouts, but no difference was seen ill LAMP-1 knockout cells. Similarly, EA invasion rate was higher for one of the double knockout clones but not for the other. Higher lysosomal exocytosis Correlated with a higher invasion rate and early lysosomal market acquisition. These findings suggest that lysosomal exocytosis is important to EA cell invasion. Also, phagolysosome maturation in knockout cell lines differed from previous results revealing that EA enter cells by a mechanism other than receptor-mediated phagocytosis. (C) 2009 Elsevier Inc. All rights reserved.
- ItemSomente MetadadadosNAADP-sensitive two-pore channels are present and functional in gastric smooth muscle cells(Churchill Livingstone, 2014-08-01) Pereira, Gustavo José da Silva [UNIFESP]; Hirata, Hanako [UNIFESP]; Garcez-do-Carmo, Lucia [UNIFESP]; Stilhano, Roberta Sessa [UNIFESP]; Ureshino, Rodrigo Portes [UNIFESP]; Medaglia, Natalia de Castro [UNIFESP]; Han, Sang Won [UNIFESP]; Churchill, Grant; Bincoletto, Claudia [UNIFESP]; Patel, Sandip; Smaili, Soraya Soubhi [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Univ Oxford; UCLNicotinic acid adenine dinucleotide phosphate (NAADP) has been identified as an important modulator of Ca2+ release from the endo-lysosomal system in a variety of cells by a new and ubiquitous class of endo-lysosomal ion channels known as the two-pore channels (TPCs). However, the role of TPCs in NAADP action in smooth muscle is not known. in the present work, we investigated the effects of NAADP in gastric smooth muscle cells and its ability to release Ca2+ by TPCs. We show that Ca2+ signals mediated by NAADP were inhibited by disrupting Ca2+ handling by either acidic organelles (using bafilomycin A1) or the Endoplasmic Reticulum (using thapsigargin, ryanodine or 2-APB). Transcripts for endogenous TPC1 and TPC2 were readily detected and recombinant TPCs localized to the endosomes and/or lysosomes. Overexpression of wild-type TPCs but not pore mutants enhanced NAADP-mediated cytosolic Ca2+ signals. Desensitizing the NAADP pathway inhibited Ca2+-responses to extracellular stimulation with carbachol but not ATP. Taken together, these results indicate that NAADP likely induces Ca2+ release from the endolysosomal system through TPCs which is subsequently amplified via the ER in an agonist-specific manner. Thus, we suggest a second messenger role for NAADP in smooth muscle cells. (C) 2014 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosVariação quantitativa dos lisossomos nas células epiteliais de fibroadenomas da glândula mamaria humana, nas fases proliferativa e secretora do ciclo menstrual(Universidade Federal de São Paulo (UNIFESP), 1991) Zamith, Roberto [UNIFESP]