JOYCE MEIRE GILIO
Projetos de Pesquisa
Unidades Organizacionais
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
2 resultados
Resultados de Busca
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- Redox modulation of thimet oligopeptidase activity by hydrogen peroxide(2017) ICIMOTO, Marcelo Y.; FERREIRA, Juliana C.; YOKOMIZO, Cesar H.; BIM, Larissa V.; MAREM, Alyne; GILIO, Joyce M.; OLIVEIRA, Vitor; NANTES, Iseli L.Thimet oligopeptidase (EC 3.4.24.15, TOP) is a cytosolic mammalian zinc protease that can process a diversity of bioactive peptides. TOP has been pointed out as one of the main postproteasomal enzymes that process peptide antigens in the MHC class I presentation route. In the present study, we describe a fine regulation of TOP activity by hydrogen peroxide (H2O2). Cells from a human embryonic kidney cell line (HEK293) underwent an ischemia/reoxygenation-like condition known to increase H2O2 production. Immediately after reoxygenation, HEK293 cells exhibited a 32% increase in TOP activity, but no TOP activity was observed 2 h after reoxygenation. In another model, recombinant rat TOP (rTOP) was challenged by H2O2 produced by rat liver mitoplasts (RLMt) alone, and in combination with antimycin A, succinate, and antimycin A plus succinate. In these conditions, rTOP activity increased 17, 30, 32 and 38%, respectively. Determination of H2O2 concentration generated in reoxygenated cells and mitoplasts suggested a possible modulation of rTOP activity dependent on the concentration of H2O2. The measure of pure rTOP activity as a function of H2O2 concentration corroborated this hypothesis. The data fitted to an asymmetrical bell-shaped curve in which the optimal activating H2O2 concentration was 1.2 nM, and the maximal inhibition (75% about the control) was 1 mu M. Contrary to the oxidation produced by aging associated with enzyme oligomerization and inhibition, H2O2 oxidation produced sulfenic acid and maintained rTOP in the monomeric form. Consistent with the involvement of rTOP in a signaling redox cascade, the H2O2-oxidized rTOP reacted with dimeric thioredoxin-1 (TRx-1) and remained covalently bound to one subunit of TRx-1.
- Genetic analysis of patients with familial and sporadic amyotrophic lateral sclerosis in a Brazilian Research Center(2017) CHADI, Gerson; MAXIMINO, Jessica Ruivo; JORGE, Frederico Mennucci De Haidar; BORBA, Fabricio Castro De; GILIO, Joyce Meire; CALLEGARO, Dagoberto; LOPES, Camila Galvao; SANTOS, Samantha Nakamura Dos; REBELO, Gabriela Natania SalesObjective: To investigate gene mutations in familial form (FALS) and sporadic form (SALS) of amyotrophic lateral sclerosis (ALS) in a highly miscegenated population. Methods: Frequencies of mutations in the C9orfF72, TARDBP, SOD1, FUS and VAPB genes were investigated in a cohort of FALS (n=39) and SALS (n=189) subjects from the Research Centre of the University of SAo Paulo School of Medicine. All patients were subjected to C9orf72 and TARDBP analyses. SOD1, FUS and VAPB were also evaluated in FALS subjects. Results: Mutations were identified in FALS (61.3%) and SALS (5.3%) patients. Mutations in C9orf72 (12.8%,>45 GGGGCC hexanucleotide repeats), VAPB (43.6%, P56S) and SOD1 (7.7%, L145S) were identified in FALS subjects. Pathogenic C9orf72 expansions (2.64%) were identified in some SALS patients. Similar changes of TARDBP were found in SALS (2.64%) but not in FALS subjects. No FUS mutations were seen in any FALS subjects. Conclusions: TARDBP and C9orf72 mutations in this cohort were similar to those found in other centres worldwide. VAPB mutation (P56S) was highly prevalent in Brazilian FALS patients.