Persistent phosphorylation of synaptic proteins following middle cerebral artery occlusion

S Matsumoto, M Shamloo, A Isshiki, Tadeusz Wieloch

Research output: Contribution to journalArticlepeer-review

14 Citations (SciVal)

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.
Original languageEnglish
Pages (from-to)1107-1113
JournalJournal of Cerebral Blood Flow and Metabolism
Volume22
Issue number9
DOIs
Publication statusPublished - 2002

Bibliographical note

The information about affiliations in this record was updated in December 2015.
The record was previously connected to the following departments: Laboratory for Experimental Brain Research (013041000)

Subject classification (UKÄ)

  • Cardiac and Cardiovascular Systems

Keywords

  • middle cerebral artery occlusion
  • tyrosine phosphorylation
  • phospho-CaMKII

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