Altered Proteins in the Hippocampus of Patients with Mesial Temporal Lobe Epilepsy

Autor(es)

Persike, Daniele Suzete ^{[1, 2]} ; Marques-Carneiro, Jose Eduardo ^{[1, 3]} ; de Lima Stein, Mariana Leao ^[4] ; Targas Yacubian, Elza Marcia ^[1] ; Centeno, Ricardo ^[1] ; Canzian, Mauro ^[5] ; da Silva Fernandes, Maria Jose ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Sao Paulo UNIFESP, Dept Neurol Neurocirurgia, Escola Paulista Med, Rua Pedro de Toledo 669, BR-04039032 Sao Paulo - Brazil

^[2] Univ Dohuk UoD, Coll Pharm, Dept Med Chem, 1006AJ, Duhok Duhok, Kurdistan Regio - Iraq

^[3] INSERM, Neuropsychol Cognit & Physiopathol Schizophrenia, U1114, 1 Pl Hop, F-67091 Strasbourg - France

^[4] Univ Fed Sao Paulo, Dept Microimunoparasito, Disciplina Biol Celular, Escola Paulista Med, BR-04039032 Sao Paulo - Brazil

^[5] FMUSP, Inst Coracao INCOR, Dept Anat Patol, BR-04039032 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PHARMACEUTICALS; v. 11, n. 4 DEC 2018.
• Citações Web of Science: 3

Resumo

Mesial temporal lobe epilepsy (MTLE) is usually associated with drug-resistant seizures and cognitive deficits. Efforts have been made to improve the understanding of the pathophysiology of MTLE for new therapies. In this study, we used proteomics to determine the differential expression of proteins in the hippocampus of patients with MTLE compared to control samples. By using the two-dimensional electrophoresis method (2-DE), the proteins were separated into spots and analyzed by LC-MS/MS. Spots that had different densitometric values for patients and controls were selected for the study. The following proteins were found to be up-regulated in patients: isoform 1 of serum albumin (ALB), proton ATPase catalytic subunit A (ATP6V1A), heat shock protein 70 (HSP70), dihydropyrimidinase-related protein 2 (DPYSL2), isoform 1 of myelin basic protein (MBP), and dihydrolipoamide S-acethyltransferase (DLAT). The protein isoform 3 of the spectrin alpha chain (SPTAN1) was down-regulated while glutathione S-transferase P (GSTP1) and protein DJ-1 (PARK7) were found only in the hippocampus of patients with MTLE. Interactome analysis of the nine proteins of interest revealed interactions with 20 other proteins, most of them involved with metabolic processes (37%), presenting catalytic activity (37%) and working as hydrolyses (25%), among others. Our results provide evidence supporting a direct link between synaptic plasticity, metabolic disturbance, oxidative stress with mitochondrial damage, the disruption of the blood-brain barrier and changes in CNS structural proteins with cell death and epileptogenesis in MTLE. Besides this, the presence of markers of cell survival indicated a compensatory mechanism. The over-expression of GSTP1 in MTLE could be related to drug-resistance. (AU)

• Processo FAPESP: 08/00068-6 - Avaliação proteômica no hipocampo humano de pacientes com epilepsia do lobo temporal e de ratos submetidos ao modelo da pilocarpina, pré-tratados e não pré-tratados com o agente neuroprotetor R-PIA.
• Beneficiário: Daniele Suzete Persike
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado