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Proteomic Expression Changes in Large Cerebral Arteries After Experimental Subarachnoid Hemorrhage in Rat Are Regulated by the MEK-ERK1/2 Pathway

Subarachnoid hemorrhage (SAH) is a serious clinical condition where leakage of blood into the subarachnoid space causes an acute rise in intracranial pressure and reduces cerebral blood flow, which may lead to delayed cerebral ischemia and poor outcome. In experimental SAH, we have previously shown...

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Autores principales: Müller, Anne H., Edwards, Alistair V.G., Larsen, Martin R., Nielsen, Janne, Warfvinge, Karin, Povlsen, Gro K., Edvinsson, Lars
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer US 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541124/
https://www.ncbi.nlm.nih.gov/pubmed/28741142
http://dx.doi.org/10.1007/s12031-017-0944-7
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author Müller, Anne H.
Edwards, Alistair V.G.
Larsen, Martin R.
Nielsen, Janne
Warfvinge, Karin
Povlsen, Gro K.
Edvinsson, Lars
author_facet Müller, Anne H.
Edwards, Alistair V.G.
Larsen, Martin R.
Nielsen, Janne
Warfvinge, Karin
Povlsen, Gro K.
Edvinsson, Lars
author_sort Müller, Anne H.
collection PubMed
description Subarachnoid hemorrhage (SAH) is a serious clinical condition where leakage of blood into the subarachnoid space causes an acute rise in intracranial pressure and reduces cerebral blood flow, which may lead to delayed cerebral ischemia and poor outcome. In experimental SAH, we have previously shown that the outcome can be significantly improved by early inhibition of the MAPK/ERK kinase/extracellular signal-regulated kinase (MEK/ERK1/2) pathway. The aim of this study was to apply mass spectrometry to investigate the overall late effects of experimental SAH on cerebrovascular protein expression. SAH was induced in rats that were treated with the MEK1/2 inhibitor U0126 or vehicle. Neurological outcome was assessed using a battery of behavioral tests. Specific protein expression of large cerebral arteries was analyzed quantitatively with high-throughput tandem mass spectrometry. SAH resulted in a marked reduction of neurological scores, which was counteracted by U0126 treatment. Mass spectrometry analysis demonstrated regulation of 184 proteins after SAH, regulations that were in part prevented by U0126 treatment. Network analysis identified several protein networks including a strong structural network centered around 14-3-3. Additionally, protein networks with functions in mRNA metabolism and protein folding were identified. Treatment with U0126 inhibited cerebral vessel wall pERK1/2 expression and significantly improved outcome of the rats. In conclusion, we show that SAH induces a broad array of specific changes in the overall protein networks in cerebral artery smooth muscle cells and suggest that this is essential for understanding the vascular pathophysiology after SAH. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12031-017-0944-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-55411242017-08-17 Proteomic Expression Changes in Large Cerebral Arteries After Experimental Subarachnoid Hemorrhage in Rat Are Regulated by the MEK-ERK1/2 Pathway Müller, Anne H. Edwards, Alistair V.G. Larsen, Martin R. Nielsen, Janne Warfvinge, Karin Povlsen, Gro K. Edvinsson, Lars J Mol Neurosci Article Subarachnoid hemorrhage (SAH) is a serious clinical condition where leakage of blood into the subarachnoid space causes an acute rise in intracranial pressure and reduces cerebral blood flow, which may lead to delayed cerebral ischemia and poor outcome. In experimental SAH, we have previously shown that the outcome can be significantly improved by early inhibition of the MAPK/ERK kinase/extracellular signal-regulated kinase (MEK/ERK1/2) pathway. The aim of this study was to apply mass spectrometry to investigate the overall late effects of experimental SAH on cerebrovascular protein expression. SAH was induced in rats that were treated with the MEK1/2 inhibitor U0126 or vehicle. Neurological outcome was assessed using a battery of behavioral tests. Specific protein expression of large cerebral arteries was analyzed quantitatively with high-throughput tandem mass spectrometry. SAH resulted in a marked reduction of neurological scores, which was counteracted by U0126 treatment. Mass spectrometry analysis demonstrated regulation of 184 proteins after SAH, regulations that were in part prevented by U0126 treatment. Network analysis identified several protein networks including a strong structural network centered around 14-3-3. Additionally, protein networks with functions in mRNA metabolism and protein folding were identified. Treatment with U0126 inhibited cerebral vessel wall pERK1/2 expression and significantly improved outcome of the rats. In conclusion, we show that SAH induces a broad array of specific changes in the overall protein networks in cerebral artery smooth muscle cells and suggest that this is essential for understanding the vascular pathophysiology after SAH. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12031-017-0944-7) contains supplementary material, which is available to authorized users. Springer US 2017-07-24 2017 /pmc/articles/PMC5541124/ /pubmed/28741142 http://dx.doi.org/10.1007/s12031-017-0944-7 Text en © The Author(s) 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Article
Müller, Anne H.
Edwards, Alistair V.G.
Larsen, Martin R.
Nielsen, Janne
Warfvinge, Karin
Povlsen, Gro K.
Edvinsson, Lars
Proteomic Expression Changes in Large Cerebral Arteries After Experimental Subarachnoid Hemorrhage in Rat Are Regulated by the MEK-ERK1/2 Pathway
title Proteomic Expression Changes in Large Cerebral Arteries After Experimental Subarachnoid Hemorrhage in Rat Are Regulated by the MEK-ERK1/2 Pathway
title_full Proteomic Expression Changes in Large Cerebral Arteries After Experimental Subarachnoid Hemorrhage in Rat Are Regulated by the MEK-ERK1/2 Pathway
title_fullStr Proteomic Expression Changes in Large Cerebral Arteries After Experimental Subarachnoid Hemorrhage in Rat Are Regulated by the MEK-ERK1/2 Pathway
title_full_unstemmed Proteomic Expression Changes in Large Cerebral Arteries After Experimental Subarachnoid Hemorrhage in Rat Are Regulated by the MEK-ERK1/2 Pathway
title_short Proteomic Expression Changes in Large Cerebral Arteries After Experimental Subarachnoid Hemorrhage in Rat Are Regulated by the MEK-ERK1/2 Pathway
title_sort proteomic expression changes in large cerebral arteries after experimental subarachnoid hemorrhage in rat are regulated by the mek-erk1/2 pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5541124/
https://www.ncbi.nlm.nih.gov/pubmed/28741142
http://dx.doi.org/10.1007/s12031-017-0944-7
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