Phosphorylation of calcium calmodulin-dependent protein kinase II following lateral fluid percussion brain injury in rats

Michael M. Folkerts, Elizabeth A. Parks, John R. Dedman, Marcia A. Kaetzel, Bruce G Lyeth, Robert F Berman

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Traumatic brain injury (TBI) can dramatically increase levels of intracellular calcium ([Ca2+]i). One consequence of increased [Ca2+]i would be altered activity and function of calcium-regulated proteins, including calcium-calmodulin-dependent protein kinase II (CaMKII), which is autophosphorylated on Thr286 (pCaMKII286) in the presence of calcium and calmodulin. Therefore, we hypothesized that TBI would result in increased levels of pCaMKII 286, and that such increases would occur early after injury in brain regions known to be damaged following lateral fluid percussion TBI (i.e., hippocampus and cortex). In order to test this hypothesis, immunostaining of CaMKII was examined in rat hippocampus and cortex after lateral fluid percussion (LFP) injury using an antibody directed against pCaMKII286. LFP injury produced a marked increase in pCaMKII286 immunostaining in the hippocampus and overlying cortex 30 min after TBI. The pattern of increased immunostaining was uneven, and unexpectedly absent in some hippocampal CA3 pyramidal neurons. This suggests that phosphatase activity may also increase following TBI, resulting in dephosphorylation of pCaMKII286 in subpopulations of CA3 pyramidal neurons. Western blotting confirmed a rapid increase in levels of pCaMKII286 at 10 and 30 min after brain injury, and that it was transient and no longer significantly elevated when examined at 3, 8, and 24 h. These results demonstrate that TBI alters the autophosphorylation state of CaMKII, an important neuronal regulator of critical cell functions, including enzyme activities, cell structure, gene expression, and neuronal plasticity, and provide a molecular mechanism that is likely to contribute to cell injury and impaired plasticity after TBI.

Original languageEnglish (US)
Pages (from-to)638-650
Number of pages13
JournalJournal of Neurotrauma
Volume24
Issue number4
DOIs
StatePublished - Apr 2007

Fingerprint

Percussion
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases
Brain Injuries
Phosphorylation
Hippocampus
Pyramidal Cells
Calcium
Wounds and Injuries
Neuronal Plasticity
Calmodulin
Traumatic Brain Injury
Phosphoric Monoester Hydrolases
Western Blotting
Gene Expression
Antibodies
Enzymes

Keywords

  • Calcium
  • CaMKII
  • Cortex
  • Hippocampus
  • Protein phosphorylation
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

Cite this

Phosphorylation of calcium calmodulin-dependent protein kinase II following lateral fluid percussion brain injury in rats. / Folkerts, Michael M.; Parks, Elizabeth A.; Dedman, John R.; Kaetzel, Marcia A.; Lyeth, Bruce G; Berman, Robert F.

In: Journal of Neurotrauma, Vol. 24, No. 4, 04.2007, p. 638-650.

Research output: Contribution to journalArticle

Folkerts, Michael M. ; Parks, Elizabeth A. ; Dedman, John R. ; Kaetzel, Marcia A. ; Lyeth, Bruce G ; Berman, Robert F. / Phosphorylation of calcium calmodulin-dependent protein kinase II following lateral fluid percussion brain injury in rats. In: Journal of Neurotrauma. 2007 ; Vol. 24, No. 4. pp. 638-650.
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