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Global Proteomic Analysis of Brain Tissues in Transient Ischemia Brain Damage in Rats

Ischemia-reperfusion injury resulting from arterial occlusion or hypotension in patients leads to tissue hypoxia with glucose deprivation, which causes endoplasmic reticulum (ER) stress and neuronal death. A proteomic approach was used to identify the differentially expressed proteins in the brain o...

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Autores principales: Chen, Jiann-Hwa, Kuo, Hsing-Chun, Lee, Kam-Fai, Tsai, Tung-Hu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490420/
https://www.ncbi.nlm.nih.gov/pubmed/26016499
http://dx.doi.org/10.3390/ijms160611873
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author Chen, Jiann-Hwa
Kuo, Hsing-Chun
Lee, Kam-Fai
Tsai, Tung-Hu
author_facet Chen, Jiann-Hwa
Kuo, Hsing-Chun
Lee, Kam-Fai
Tsai, Tung-Hu
author_sort Chen, Jiann-Hwa
collection PubMed
description Ischemia-reperfusion injury resulting from arterial occlusion or hypotension in patients leads to tissue hypoxia with glucose deprivation, which causes endoplasmic reticulum (ER) stress and neuronal death. A proteomic approach was used to identify the differentially expressed proteins in the brain of rats following a global ischemic stroke. The mechanisms involved the action in apoptotic and ER stress pathways. Rats were treated with ischemia-reperfusion brain injuries by the bilateral occlusion of the common carotid artery. The cortical neuron proteins from the stroke animal model (SAM) and the control rats were separated using two-dimensional gel electrophoresis (2-DE) to purify and identify the protein profiles. Our results demonstrated that the SAM rats experienced brain cell death in the ischemic core. Fifteen proteins were expressed differentially between the SAM rats and control rats, which were assayed and validated in vivo and in vitro. Interestingly, the set of differentially expressed, down-regulated proteins included catechol O-methyltransferase (COMT) and cathepsin D (CATD), which are implicated in oxidative stress, inflammatory response and apoptosis. After an ischemic stroke, one protein spot, namely the calretinin (CALB2) protein, showed increased expression. It mediated the effects of SAM administration on the apoptotic and ER stress pathways. Our results demonstrate that the ischemic injury of neuronal cells increased cell cytoxicity and apoptosis, which were accompanied by sustained activation of the IRE1-alpha/TRAF2, JNK1/2, and p38 MAPK pathways. Proteomic analysis suggested that the differential expression of CALB2 during a global ischemic stroke could be involved in the mechanisms of ER stress-induced neuronal cell apoptosis, which occurred via IRE1-alpha/TRAF2 complex formation, with activation of JNK1/2 and p38 MAPK. Based on these results, we also provide the molecular evidence supporting the ischemia-reperfusion-related neuronal injury.
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spelling pubmed-44904202015-07-07 Global Proteomic Analysis of Brain Tissues in Transient Ischemia Brain Damage in Rats Chen, Jiann-Hwa Kuo, Hsing-Chun Lee, Kam-Fai Tsai, Tung-Hu Int J Mol Sci Article Ischemia-reperfusion injury resulting from arterial occlusion or hypotension in patients leads to tissue hypoxia with glucose deprivation, which causes endoplasmic reticulum (ER) stress and neuronal death. A proteomic approach was used to identify the differentially expressed proteins in the brain of rats following a global ischemic stroke. The mechanisms involved the action in apoptotic and ER stress pathways. Rats were treated with ischemia-reperfusion brain injuries by the bilateral occlusion of the common carotid artery. The cortical neuron proteins from the stroke animal model (SAM) and the control rats were separated using two-dimensional gel electrophoresis (2-DE) to purify and identify the protein profiles. Our results demonstrated that the SAM rats experienced brain cell death in the ischemic core. Fifteen proteins were expressed differentially between the SAM rats and control rats, which were assayed and validated in vivo and in vitro. Interestingly, the set of differentially expressed, down-regulated proteins included catechol O-methyltransferase (COMT) and cathepsin D (CATD), which are implicated in oxidative stress, inflammatory response and apoptosis. After an ischemic stroke, one protein spot, namely the calretinin (CALB2) protein, showed increased expression. It mediated the effects of SAM administration on the apoptotic and ER stress pathways. Our results demonstrate that the ischemic injury of neuronal cells increased cell cytoxicity and apoptosis, which were accompanied by sustained activation of the IRE1-alpha/TRAF2, JNK1/2, and p38 MAPK pathways. Proteomic analysis suggested that the differential expression of CALB2 during a global ischemic stroke could be involved in the mechanisms of ER stress-induced neuronal cell apoptosis, which occurred via IRE1-alpha/TRAF2 complex formation, with activation of JNK1/2 and p38 MAPK. Based on these results, we also provide the molecular evidence supporting the ischemia-reperfusion-related neuronal injury. MDPI 2015-05-26 /pmc/articles/PMC4490420/ /pubmed/26016499 http://dx.doi.org/10.3390/ijms160611873 Text en © 2015 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Chen, Jiann-Hwa
Kuo, Hsing-Chun
Lee, Kam-Fai
Tsai, Tung-Hu
Global Proteomic Analysis of Brain Tissues in Transient Ischemia Brain Damage in Rats
title Global Proteomic Analysis of Brain Tissues in Transient Ischemia Brain Damage in Rats
title_full Global Proteomic Analysis of Brain Tissues in Transient Ischemia Brain Damage in Rats
title_fullStr Global Proteomic Analysis of Brain Tissues in Transient Ischemia Brain Damage in Rats
title_full_unstemmed Global Proteomic Analysis of Brain Tissues in Transient Ischemia Brain Damage in Rats
title_short Global Proteomic Analysis of Brain Tissues in Transient Ischemia Brain Damage in Rats
title_sort global proteomic analysis of brain tissues in transient ischemia brain damage in rats
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4490420/
https://www.ncbi.nlm.nih.gov/pubmed/26016499
http://dx.doi.org/10.3390/ijms160611873
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