Navegando por Palavras-chave "tRNA"

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    The mutations m.5628T > C and m18348A > G in single muscle fibers of a patient with chronic progressive external ophthalmoplegia
    (Elsevier B.V., 2012-09-15) Gamba, Juliana [UNIFESP]; Kiyomoto, Beatriz Hitomi [UNIFESP]; Oliveira, Acary Souza Bulle [UNIFESP]; Gabbai, Alberto Alain [UNIFESP]; Schmidt, Beny [UNIFESP]; Tengan, Celia Harumi [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    We identified a double mutation in a patient with chronic progressive external ophthalmoplegia, located in the tRNA(Ala) (m.5628T > C) and tRNA(LYs) (m.8348A > G) genes. Both mutations were previously described separately and considered pathogenic, however the same mutations were also reported as polymorphisms or phenotype modulator. We analyzed the proportion of each mutation in isolated muscle fibers by single fiber-polymerase chain reaction to investigate the contribution of each mutation to mitochondrial deficiency. Our findings demonstrated that the mutations were heteroplasmic in skeletal muscle and both mutations were present in all single muscle fibers. the proportions of the m.5628T > C mutation were not significantly different between normal and cytochrome-c-oxidase (COX) deficient fibers. However, a significant higher proportion of the m.8348A > G mutation was observed in COX deficient fibers. Homoplasmic m.8348A > G was only observed in COX negative fibers. in conclusion, we provide a piece of evidence toward the pathogenicity of the m.8348A > G mutation and suggest that m.5628T > C is probably a neutral polymorphism. (c) 2012 Elsevier B.V. All rights reserved.
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    Relação de alterações conformacionais da prolil oligopeptidase devido a interação com a α – sinucleína
    (Universidade Federal de São Paulo (UNIFESP), 2019-09-26) Santos, Gabriel Silva [UNIFESP]; Oliveira, Vitor Marcelo Silveira Bueno Brandao De [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    Prolyl oligopeptidase (EC 3.4.21.26, POP) is a serine peptidase, involved in the metabolism of neuropeptides and peptide hormones. In vitro and in vivo studies show that POP interacts with alpha synuclein (syn) by accelerating the aggregation of this protein, although when prolyl oligopeptidase is inhibited, syn aggregation is reduced. This mechanism for POP's participation in syn aggregation is totally unknown. The structure of POP does not allow peptides larger than 30 amino acid residues or proteins to reach their active center. Data from the literature show that POP presents an open (catalytic and regulatory domain shift with active center exposure) and a closed (catalytic and regulatory domain approach) conformation. The overall objective of this project was to study this possible "open and close" movement that may occur in POP due to interaction with substrates or inhibitors, and the implication of this conformational change in interaction with alpha synuclein. For this purpose, spectroscopic probes were used, when nearby they have characteristic fluorescence emission, excimer, in order to evaluate the conformational movements of POP and the possible implication of these movements in the interaction with syn. To validate the applied methodology, we used Thimet Oligopeptidase (TOP) a protein widely studied in our research group. The use of TOP provided important data for the use of spectroscopic probes showing that the separation of oligomeric species is fundamental for the analyzes studied here. The proteins with the spectroscopic probes showed activity, indicating that the tertiary structure was not impaired and consequently its function. Probe approximation with increasing guanidine chloride concentration showing probe spacing and excimer disappearance were evaluated. In addition, we evaluated by circular dichroism the POP - syn interaction and the hydrolysis profile of POP in the presence of syn. Interestingly, the high concentration of syn hinders substrate access to the active center, and the interaction between proteins occurs a change in secondary structure