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

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

Author Rodrigues Simoes, Priscila Santos Autor UNIFESP Google Scholar
Visniauskas, Bruna Autor UNIFESP Google Scholar
Perosa, Sandra Regina Autor UNIFESP Google Scholar
Yacubian, Elza Márcia Targas Autor UNIFESP Google Scholar
Centeno, Ricardo Autor UNIFESP Google Scholar
Canzian, Mauro Google Scholar
Lopes-Cendes, Iscia Google Scholar
Maurer Morelli, Claudia Vianna Google Scholar
Carrete, Henrique Autor UNIFESP Google Scholar
Cavalheiro, Esper Abrão Autor UNIFESP Google Scholar
Tufik, Sergio Autor UNIFESP Google Scholar
Chagas, Jair Ribeiro Autor UNIFESP Google Scholar
Naffah-Mazzacoratti, Maria da Graca Autor UNIFESP Google Scholar
Institution Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Universidade Estadual de Campinas (UNICAMP)
Abstract 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.
Keywords Temporal lobe epilepsy
Mesial sclerosis
Thimet oligopeptidase
Language English
Date 2014-05-01
Published in Epilepsia. Hoboken: Wiley-Blackwell, v. 55, n. 5, p. 754-762, 2014.
ISSN 0013-9580 (Sherpa/Romeo, impact factor)
Publisher Wiley-Blackwell
Extent 754-762
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000336623200022

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