Signal transduction in cerebral arteries after subarachnoid hemorrhage-a phosphoproteomic approach
(2013) In Journal of Cerebral Blood Flow and Metabolism 33(8). p.1259-1269- Abstract
- After subarachnoid hemorrhage (SAH), pathologic changes in cerebral arteries contribute to delayed cerebral ischemia and poor outcome. We hypothesize such changes are triggered by early intracellular signals, targeting of which may prevent SAH-induced vasculopathy. We performed an unbiased quantitative analysis of early SAH-induced phosphorylations in cerebral arteries and evaluated identified signaling components as targets for prevention of delayed vasculopathy and ischemia. Labeled phosphopeptides from rat cerebral arteries were quantified by high-resolution tandem mass spectrometry. Selected SAH-induced phosphorylations were validated by immunoblotting and monitored over a 24-hour time course post SAH. Moreover, inhibition of key... (More)
- After subarachnoid hemorrhage (SAH), pathologic changes in cerebral arteries contribute to delayed cerebral ischemia and poor outcome. We hypothesize such changes are triggered by early intracellular signals, targeting of which may prevent SAH-induced vasculopathy. We performed an unbiased quantitative analysis of early SAH-induced phosphorylations in cerebral arteries and evaluated identified signaling components as targets for prevention of delayed vasculopathy and ischemia. Labeled phosphopeptides from rat cerebral arteries were quantified by high-resolution tandem mass spectrometry. Selected SAH-induced phosphorylations were validated by immunoblotting and monitored over a 24-hour time course post SAH. Moreover, inhibition of key phosphoproteins was performed. Major SAH-induced phosphorylations were observed on focal adhesion complexes, extracellular regulated kinase 1/2 (ERK1/2), calcium calmodulin-dependent kinase II, signal transducer and activator of transcription (STAT3) and c-Jun, the latter two downstream of ERK1/2. Inhibition of ERK1/2 6-hour post SAH prevented increases in cerebrovascular constrictor receptors, matrix metalloprotease-9, wall thickness, and improved neurologic outcome. STAT3 inhibition partially mimicked these effects. The study shows that quantitative mass spectrometry is a strong approach to study in vivo vascular signaling. Moreover, it shows that targeting of ERK1/2 prevents delayed pathologic changes in cerebral arteries and improves outcome, and identifies SAH-induced signaling components downstream and upstream of ERK1/2. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/4050347
- author
- Parker, Benjamin L. ; Larsen, Martin Rossel ; Edvinsson, Lars LU and Povlsen, Gro Klitgaard
- organization
- publishing date
- 2013
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- cerebral arteries, ERK1/2, phosphoproteomics, STAT3, subarachnoid, hemorrhage
- in
- Journal of Cerebral Blood Flow and Metabolism
- volume
- 33
- issue
- 8
- pages
- 1259 - 1269
- publisher
- Nature Publishing Group
- external identifiers
-
- wos:000322570000016
- scopus:84881153204
- pmid:23715060
- ISSN
- 1559-7016
- DOI
- 10.1038/jcbfm.2013.78
- language
- English
- LU publication?
- yes
- id
- 500ca352-f542-4fb2-97ec-11f367856cec (old id 4050347)
- date added to LUP
- 2016-04-01 14:42:56
- date last changed
- 2024-01-10 07:39:23
@article{500ca352-f542-4fb2-97ec-11f367856cec,
abstract = {{After subarachnoid hemorrhage (SAH), pathologic changes in cerebral arteries contribute to delayed cerebral ischemia and poor outcome. We hypothesize such changes are triggered by early intracellular signals, targeting of which may prevent SAH-induced vasculopathy. We performed an unbiased quantitative analysis of early SAH-induced phosphorylations in cerebral arteries and evaluated identified signaling components as targets for prevention of delayed vasculopathy and ischemia. Labeled phosphopeptides from rat cerebral arteries were quantified by high-resolution tandem mass spectrometry. Selected SAH-induced phosphorylations were validated by immunoblotting and monitored over a 24-hour time course post SAH. Moreover, inhibition of key phosphoproteins was performed. Major SAH-induced phosphorylations were observed on focal adhesion complexes, extracellular regulated kinase 1/2 (ERK1/2), calcium calmodulin-dependent kinase II, signal transducer and activator of transcription (STAT3) and c-Jun, the latter two downstream of ERK1/2. Inhibition of ERK1/2 6-hour post SAH prevented increases in cerebrovascular constrictor receptors, matrix metalloprotease-9, wall thickness, and improved neurologic outcome. STAT3 inhibition partially mimicked these effects. The study shows that quantitative mass spectrometry is a strong approach to study in vivo vascular signaling. Moreover, it shows that targeting of ERK1/2 prevents delayed pathologic changes in cerebral arteries and improves outcome, and identifies SAH-induced signaling components downstream and upstream of ERK1/2.}},
author = {{Parker, Benjamin L. and Larsen, Martin Rossel and Edvinsson, Lars and Povlsen, Gro Klitgaard}},
issn = {{1559-7016}},
keywords = {{cerebral arteries; ERK1/2; phosphoproteomics; STAT3; subarachnoid; hemorrhage}},
language = {{eng}},
number = {{8}},
pages = {{1259--1269}},
publisher = {{Nature Publishing Group}},
series = {{Journal of Cerebral Blood Flow and Metabolism}},
title = {{Signal transduction in cerebral arteries after subarachnoid hemorrhage-a phosphoproteomic approach}},
url = {{http://dx.doi.org/10.1038/jcbfm.2013.78}},
doi = {{10.1038/jcbfm.2013.78}},
volume = {{33}},
year = {{2013}},
}