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Persistent phosphorylation of synaptic proteins following middle cerebral artery occlusion

Matsumoto, S; Shamloo, M; Isshiki, A and Wieloch, Tadeusz LU (2002) In Journal of Cerebral Blood Flow and Metabolism 22(9). p.1107-1113
Abstract
Transient cerebral ischemia following I to 2 hours of middle cerebral artery occlusion (MCAO) in the rat leads to infarction, which can be diminished by synaptic transmission modulators, implying aberrant cell signaling in the pathogenetic process. The authors report here changes in the levels of tyrosine phosphorylated proteins (PTyr) and calcium calmodulin kinase II (CaMKII) phosphorylation of Thr 286, in synaptosomal, particulate, and cytosolic fractions of different cortical areas following I or 2 hours of MCAO, or 2 hours of MCAO followed by 2 hours of reperfusion. At the end of 2-hour MCAO, PTyr, and in particular the pp180, indicative of NR2A/B subunit, increased in the synaptosomal fraction in less ischemic areas while it decreased... (More)
Transient cerebral ischemia following I to 2 hours of middle cerebral artery occlusion (MCAO) in the rat leads to infarction, which can be diminished by synaptic transmission modulators, implying aberrant cell signaling in the pathogenetic process. The authors report here changes in the levels of tyrosine phosphorylated proteins (PTyr) and calcium calmodulin kinase II (CaMKII) phosphorylation of Thr 286, in synaptosomal, particulate, and cytosolic fractions of different cortical areas following I or 2 hours of MCAO, or 2 hours of MCAO followed by 2 hours of reperfusion. At the end of 2-hour MCAO, PTyr, and in particular the pp180, indicative of NR2A/B subunit, increased in the synaptosomal fraction in less ischemic areas while it decreased in more severe ischemic regions. During reperfusion, phosphorylation increased at least 2 fold in, reperfused areas, During 2 hours of MCAO, the phosphorylation of CaMKII increased 8- to 10-fold in the synaptosomal fraction in all ischemic brain regions. During reperfusion, the phospho-CaMKII levels remained elevated by approximately 300%, compared with the contralateral hemisphere (control). There was no increase in phospho-CaMKII in the cytosolic fraction at any time during, or following ischemia in any of the brain regions examined. The authors conclude that both tyrosine kinase coupled pathways, as well as CaMKII-mediated cellular processes associated with synaptic activity, are strongly activated during and particularly following MCAO. These results support the hypothesis that aberrant cell signaling may contribute to ischemic cell death and dysfunction, and that selective modulators of cell signaling may be targets for pharmacological intervention against ischemic brain damage. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
middle cerebral artery occlusion, tyrosine phosphorylation, phospho-CaMKII
in
Journal of Cerebral Blood Flow and Metabolism
volume
22
issue
9
pages
1107 - 1113
publisher
Nature Publishing Group
external identifiers
  • pmid:12218416
  • wos:000177919400008
  • scopus:0036713959
ISSN
1559-7016
DOI
10.1097/00004647-200209000-00008
language
English
LU publication?
yes
id
b6a04e6c-bdcb-4f92-bf1a-e9d010fcae4c (old id 329187)
date added to LUP
2007-11-02 11:32:44
date last changed
2017-02-26 04:11:23
@article{b6a04e6c-bdcb-4f92-bf1a-e9d010fcae4c,
  abstract     = {Transient cerebral ischemia following I to 2 hours of middle cerebral artery occlusion (MCAO) in the rat leads to infarction, which can be diminished by synaptic transmission modulators, implying aberrant cell signaling in the pathogenetic process. The authors report here changes in the levels of tyrosine phosphorylated proteins (PTyr) and calcium calmodulin kinase II (CaMKII) phosphorylation of Thr 286, in synaptosomal, particulate, and cytosolic fractions of different cortical areas following I or 2 hours of MCAO, or 2 hours of MCAO followed by 2 hours of reperfusion. At the end of 2-hour MCAO, PTyr, and in particular the pp180, indicative of NR2A/B subunit, increased in the synaptosomal fraction in less ischemic areas while it decreased in more severe ischemic regions. During reperfusion, phosphorylation increased at least 2 fold in, reperfused areas, During 2 hours of MCAO, the phosphorylation of CaMKII increased 8- to 10-fold in the synaptosomal fraction in all ischemic brain regions. During reperfusion, the phospho-CaMKII levels remained elevated by approximately 300%, compared with the contralateral hemisphere (control). There was no increase in phospho-CaMKII in the cytosolic fraction at any time during, or following ischemia in any of the brain regions examined. The authors conclude that both tyrosine kinase coupled pathways, as well as CaMKII-mediated cellular processes associated with synaptic activity, are strongly activated during and particularly following MCAO. These results support the hypothesis that aberrant cell signaling may contribute to ischemic cell death and dysfunction, and that selective modulators of cell signaling may be targets for pharmacological intervention against ischemic brain damage.},
  author       = {Matsumoto, S and Shamloo, M and Isshiki, A and Wieloch, Tadeusz},
  issn         = {1559-7016},
  keyword      = {middle cerebral artery occlusion,tyrosine phosphorylation,phospho-CaMKII},
  language     = {eng},
  number       = {9},
  pages        = {1107--1113},
  publisher    = {Nature Publishing Group},
  series       = {Journal of Cerebral Blood Flow and Metabolism},
  title        = {Persistent phosphorylation of synaptic proteins following middle cerebral artery occlusion},
  url          = {http://dx.doi.org/10.1097/00004647-200209000-00008},
  volume       = {22},
  year         = {2002},
}