Advanced

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 LU ; Povlsen, Gro K and Edvinsson, Lars LU (2017) In Journal of Molecular Neuroscience
Abstract

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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
epub
subject
keywords
Animal model, Mass spectrometry, MEK1/2 inhibition, Proteomics, SAH
in
Journal of Molecular Neuroscience
pages
15 pages
publisher
Humana Press
external identifiers
  • scopus:85025710201
  • wos:000407356600013
ISSN
0895-8696
DOI
10.1007/s12031-017-0944-7
language
English
LU publication?
yes
id
c74087b1-a61d-47fa-81f8-c5d652d36abb
date added to LUP
2017-08-02 09:22:23
date last changed
2017-09-18 11:40:46
@article{c74087b1-a61d-47fa-81f8-c5d652d36abb,
  abstract     = {<p>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.</p>},
  author       = {Müller, Anne H and Edwards, Alistair V G and Larsen, Martin R and Nielsen, Janne and Warfvinge, Karin and Povlsen, Gro K and Edvinsson, Lars},
  issn         = {0895-8696},
  keyword      = {Animal model,Mass spectrometry,MEK1/2 inhibition,Proteomics,SAH},
  language     = {eng},
  month        = {07},
  pages        = {15},
  publisher    = {Humana Press},
  series       = {Journal of Molecular Neuroscience},
  title        = {Proteomic Expression Changes in Large Cerebral Arteries After Experimental Subarachnoid Hemorrhage in Rat Are Regulated by the MEK-ERK1/2 Pathway},
  url          = {http://dx.doi.org/10.1007/s12031-017-0944-7},
  year         = {2017},
}