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      Identification of Proteins Differentially Expressed in the Striatum by Melatonin in a Middle Cerebral Artery Occlusion Rat Model—a Proteomic and in silico Approach

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          Ischemic stroke is characterized by permanent or transient obstruction of blood flow, which initiates a cascading pathological process, starting from acute ATP loss to subsequent membrane depolarization, glutamate excitotoxicity, and calcium overload. Melatonin is a potent antioxidant that exerts protective effects in different experimental stroke models. In this study, melatonin effects were demonstrated by a proteomic and in silico approach. The proteomic study identified differentially expressed proteins by 2D gel electrophoresis in the striatum 24 h after middle cerebral artery occlusion. Proteomic analysis revealed several proteins with aberrant expression and was validated by western blot and immunofluorescence analysis. Homology modeling was performed to build 3D structures for γ-enolase, thioredoxin (TRX), and heat shock 60 (HSP60) by the template crystal structures using a protein data bank as a sequence database. The structure refinement of each model was achieved by energy minimization via molecular dynamic simulation, and the generated models were further assessed for stability by Procheck and ProSA. The models were processed for docking analysis using AutoDock Vina, and post-docking analysis was determined by discovery studio. The proteomic study showed decreased expression of γ-enolase, TRX, and protein phosphatase 2A subunit B and increased expression of collapsin response mediator protein 2 and HSP60 in the striatum after ischemic injury. Treatment with melatonin modulated the expression profiles of these proteins. This study demonstrated the neuroprotective role of melatonin in the ischemic striatum using a proteomic and in silico approach. Collectively, melatonin may act in a multimechanistic way by modulating the expression of several proteins in the ischemic striatum.

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                Author and article information

                Front Neurosci
                Front Neurosci
                Front. Neurosci.
                Frontiers in Neuroscience
                Frontiers Media S.A.
                10 December 2018
                : 12
                1Division of Applied Life Science (BK 21), College of Natural Science, Gyeongsang National University , Jinju, South Korea
                2Department of Pharmacology, Riphah Institute of Pharmaceutical Sciences, Riphah International University Islamabad , Rawalpindi, Pakistan
                3Department of Pharmacy, Faculty of Life Science, Sarhad University of Science and Information Technology , Peshawar, Pakistan
                4Department of Anatomy, College of Veterinary Medicine, Research Institute of Life Science, Gyeongsang National University , Jinju, South Korea
                Author notes

                Edited by: Francisco Lopez-Munoz, Universidad Camilo José Cela, Spain

                Reviewed by: Anwen Shao, Second Affiliated Hospital, Zhejiang University School of Medicine, China; Alejandro Romero, Complutense University of Madrid, Spain

                *Correspondence: Myeong Ok Kim, mokim@ ; mokim@

                These authors have contributed equally to this work

                This article was submitted to Neuropharmacology, a section of the journal Frontiers in Neuroscience

                Copyright © 2018 Shah, Zeb, Ali, Muhammad, Faheem, Alam, Saeed, Koh, Lee and Kim.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                Page count
                Figures: 6, Tables: 2, Equations: 0, References: 84, Pages: 15, Words: 0
                Original Research


                melatonin, striatum, ischemic stroke, docking, neuroprotection


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