Application of proteomic approaches to assess the effect of anti-epileptic drug on seizure foci

doi:10.5246/jcps.2020.01.002

Abstract

Abstract:

Epilepsy is one of the most common neurological disorders characterized by epileptic seizures. The anti-epileptic drugs (AEDs) are the main form of treatment for people with epilepsy. Classically, people thought that AEDs modify the activities of ion channels to suppress epileptic seizures. However, accumulating evidence suggests that targeting at ion channels cannot completely account for the numerous effects of the AEDs on its broad clinical activity in epileptic patients. In our study, proteomic methods were used to quantify the proteome of hippocampal tissues from patients who were treated or not treated by AEDs (Carbamazepine). Further bioinformatics methods, including Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, were utilized to analyze the differences between two patient groups. We found that more than 400 proteins, including metabolism and immune related proteins, had a higher expression level in the carbamazepine-treated group compared with the controls. These altered proteins were considered to be involved in many different biological pathways. Among these pathways, immune-system related pathway modulated by complement C3 and microglia was highly remarkable, which regulated the synapses elimination in physiological condition. In epilepsy, the carbamazepine induced up-regulation of complement C3 might decrease the abnormal synaptic connections between neurons and thus contribute to the therapeutic role of carbamazepine. The results of our study suggested that apart from ion channels, carbamazepine exerted numerous effects on human epileptic foci, which might be the fundamental mechanisms of AEDs for treatment, adverse-effects and pharmacoresistance of epilepsy.

Key words: Carbamazepine, Proteomics, Complement-related synaptic modification, Glutathione S-transferase enzyme

CLC Number:

R965

Supporting:

Figure S1. Schematic of possible mechanism of GST-m in AED-induced intractable epilepsy. (A)Enzymatic role of GST-m cooperating with MRP (other kinds of drug efflux transporters are also possible). (B) Schematic of non-enzymatic (regulatory) role of GST-m combined with its enzymatic role in AED-induced drug resistance of epilepsy.

Table S1. Eight proteins that participate in the biosynthesis of antibiotics were listed.

Yujing Song, Xuyang Zhao, Qian Chen, Yan Song, Wanyu Lei, Yuxin Yin, Weining Ma, Zhuo Huang. Application of proteomic approaches to assess the effect of anti-epileptic drug on seizure foci[J]. Journal of Chinese Pharmaceutical Sciences, 2020, 29(1): 13-28.

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