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Alterations in the Cerebral Microvascular Proteome Expression Profile After Transient Global Cerebral Ischemia in Rat

Spray, Stine; Johansson, Sara E. LU ; Edwards, Alistair V G; Larsen, Martin R.; Radziwon-Balicka, Aneta; Povlsen, Gro K. and Edvinsson, Lars LU (2017) In Journal of Molecular Neuroscience 61(3). p.396-411
Abstract
This study aimed at obtaining an in-depth mapping of expressional changes of the cerebral microvasculature after transient global cerebral ischemia (GCI) and the impact on these GCI-induced expressional changes of post-GCI treatment with a mitogen-activated protein kinase kinase (MEK1/2) inhibitor. GCI was induced in male Wistar rats followed by treatment with either vehicle or the MEK1/2 inhibitor U0126 every 12 h post-GCI. Seventy-two hours after GCI or sham surgery, the cerebral microvasculature was isolated and the protein content analysed with state-of-the-art mass spectrometry. The proteomic profile of the isolated cerebral microvasculature 72 h after GCI (compared to sham) indicated that the main expressional changes could be... (More)
This study aimed at obtaining an in-depth mapping of expressional changes of the cerebral microvasculature after transient global cerebral ischemia (GCI) and the impact on these GCI-induced expressional changes of post-GCI treatment with a mitogen-activated protein kinase kinase (MEK1/2) inhibitor. GCI was induced in male Wistar rats followed by treatment with either vehicle or the MEK1/2 inhibitor U0126 every 12 h post-GCI. Seventy-two hours after GCI or sham surgery, the cerebral microvasculature was isolated and the protein content analysed with state-of-the-art mass spectrometry. The proteomic profile of the isolated cerebral microvasculature 72 h after GCI (compared to sham) indicated that the main expressional changes could be divided into nine categories: (1) cellular respiration, (2) remodelling of the extracellular matrix, (3) decreased contractile phenotype, (4) clathrin-mediated endocytosis, (5) ribosomal activity, (6) expression of chromatin structure-related proteins, (7) altered synaptic activity, (8) altered G-protein signalling and (9) instability of the membrane potential. Treatment with U0126 partly normalized the expression of one or more of the proteins in all nine categories. Flow cytometry confirmed key findings from the proteome such as upregulation of the extracellular proteins lamininβ2 and nidogen2 (p <0.05) after GCI. These results provide valuable molecular insight into the broad and complex expressional changes in the cerebral microvasculature after GCI and the effect of early MEK1/2 inhibitor treatment on these changes. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cerebral microvasculature, Extracellular matrix remodelling, Global cerebral ischemia, MEK1/2 inhibitor treatment, Proteomics
in
Journal of Molecular Neuroscience
volume
61
issue
3
pages
396 - 411
publisher
Humana Press
external identifiers
  • scopus:85001784661
  • wos:000396264700012
ISSN
0895-8696
DOI
10.1007/s12031-016-0875-8
language
English
LU publication?
yes
id
f26d9f69-3181-429a-88f8-056aac66ddd8
date added to LUP
2016-12-23 08:53:22
date last changed
2018-01-07 11:42:33
@article{f26d9f69-3181-429a-88f8-056aac66ddd8,
  abstract     = {This study aimed at obtaining an in-depth mapping of expressional changes of the cerebral microvasculature after transient global cerebral ischemia (GCI) and the impact on these GCI-induced expressional changes of post-GCI treatment with a mitogen-activated protein kinase kinase (MEK1/2) inhibitor. GCI was induced in male Wistar rats followed by treatment with either vehicle or the MEK1/2 inhibitor U0126 every 12 h post-GCI. Seventy-two hours after GCI or sham surgery, the cerebral microvasculature was isolated and the protein content analysed with state-of-the-art mass spectrometry. The proteomic profile of the isolated cerebral microvasculature 72 h after GCI (compared to sham) indicated that the main expressional changes could be divided into nine categories: (1) cellular respiration, (2) remodelling of the extracellular matrix, (3) decreased contractile phenotype, (4) clathrin-mediated endocytosis, (5) ribosomal activity, (6) expression of chromatin structure-related proteins, (7) altered synaptic activity, (8) altered G-protein signalling and (9) instability of the membrane potential. Treatment with U0126 partly normalized the expression of one or more of the proteins in all nine categories. Flow cytometry confirmed key findings from the proteome such as upregulation of the extracellular proteins lamininβ2 and nidogen2 (p &lt;0.05) after GCI. These results provide valuable molecular insight into the broad and complex expressional changes in the cerebral microvasculature after GCI and the effect of early MEK1/2 inhibitor treatment on these changes.},
  author       = {Spray, Stine and Johansson, Sara E. and Edwards, Alistair V G and Larsen, Martin R. and Radziwon-Balicka, Aneta and Povlsen, Gro K. and Edvinsson, Lars},
  issn         = {0895-8696},
  keyword      = {Cerebral microvasculature,Extracellular matrix remodelling,Global cerebral ischemia,MEK1/2 inhibitor treatment,Proteomics},
  language     = {eng},
  number       = {3},
  pages        = {396--411},
  publisher    = {Humana Press},
  series       = {Journal of Molecular Neuroscience},
  title        = {Alterations in the Cerebral Microvascular Proteome Expression Profile After Transient Global Cerebral Ischemia in Rat},
  url          = {http://dx.doi.org/10.1007/s12031-016-0875-8},
  volume       = {61},
  year         = {2017},
}