Expression and activity of thimet oligopeptidase (TOP) are modified in the hippocampus of subjects with temporal lobe epilepsy (TLE)

Rodrigues Simoes, Priscila Santos [UNIFESP]; Visniauskas, Bruna [UNIFESP]; Perosa, Sandra Regina [UNIFESP]; Yacubian, Elza Márcia Targas [UNIFESP]; Centeno, Ricardo [UNIFESP]; Canzian, Mauro; Lopes-Cendes, Iscia; Maurer Morelli, Claudia Vianna; Carrete, Henrique [UNIFESP]; Cavalheiro, Esper Abrão [UNIFESP]; Tufik, Sergio [UNIFESP]; Chagas, Jair Ribeiro [UNIFESP]; Naffah-Mazzacoratti, Maria da Graca [UNIFESP]

Expression and activity of thimet oligopeptidase (TOP) are modified in the hippocampus of subjects with temporal lobe epilepsy (TLE)

Data

2014-05-01

Autores

Rodrigues Simoes, Priscila Santos

Visniauskas, Bruna

Perosa, Sandra Regina

Yacubian, Elza Márcia Targas

Centeno, Ricardo

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Artigo

Resumo

ObjectiveThimet oligopeptidase (TOP) is a metalloprotease that has been associated with peptide processing in several nervous system structures, and its substrates include several peptides such as bradykinin, amyloid beta (A), and major histocompatibility complex (MHC) class I molecules. As shown previously by our research group, patients with temporal lobe epilepsy (TLE) have a high level of kinin receptors as well as kallikrein, a kinin-releasing enzyme, in the hippocampus.MethodsIn this study, we evaluated the expression, distribution, and activity of TOP in the hippocampus of patients with TLE and autopsy-control tissues, through reverse-transcription polymerase chain reaction (RT-PCR), enzymatic activity, Western blot, and immunohistochemistry. in addition, hippocampi of rats were analyzed using the pilocarpine-induced epilepsy model. Animals were grouped according to the epilepsy phases defined in the model as acute, silent, and chronic.ResultsIncreased TOP mRNA expression, decreased protein levels and enzymatic activity were observed in tissues of patients, compared to control samples. in addition, decreased TOP distribution was also visualized by immunohistochemistry. Similar results were observed in tissues of rats during the acute phase of epilepsy model. However, increased TOP mRNA expression and no changes in immunoreactivity were found in the silent phase, whereas increased TOP mRNA expression and increased enzymatic activity were observed in the chronic phase.SignificanceThe results show that these alterations could be related to a failure in the mechanisms involved in clearance of inflammatory peptides in the hippocampus, suggesting an accumulation of potentially harmful substances in nervous tissue such as A, bradykinin, and antigenic peptides. These accumulations could be related to hippocampal inflammation observed in TLE subjects.

Citação

Epilepsia. Hoboken: Wiley-Blackwell, v. 55, n. 5, p. 754-762, 2014.