DAPK catalytic activity in the hippocampus increases during the recovery phase in an animal model of brain hypoxic-ischemic injury

Andrew M. Schumacher, Anastasia V. Velentza, D. Martin Watterson, Mark S. Wainwright*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Death-associated protein kinase (DAPK) is a pro-apoptotic, calmodulin (CaM)-regulated protein kinase whose mRNA levels increase following cerebral ischemia. However, the relationship between DAPK catalytic activity and cerebral ischemia is not known. This knowledge is critical as DAPK function is dependent on the catalytic activity of its kinase domain. Consequently, we examined DAPK catalytic activity in a rat model of neonatal cerebral hypoxia-ischemia (HI). An increase in DAPK specific activity was found in homogenates of the hippocampus from the injured right hemisphere, compared to the uninjured left hemisphere, 7 days after injury. The results raised the possibility that an upregulation of DAPK activity might be associated with the recovery phase of HI, during which neuronal repair and differentiation are initiated. Therefore, we examined the change of DAPK in an experimentally tractable cell culture model of neuronal differentiation. We found that DAPK catalytic activity and protein levels increase after nerve growth factor (NGF)-induced differentiation of rat PC12 cells. These results suggest that DAPK may have a previously unappreciated role in neuronal development or recovery from injury, and that potential future therapies targeting DAPK should consider a restricted time window.

Original languageEnglish (US)
Pages (from-to)128-137
Number of pages10
JournalBiochimica et Biophysica Acta - Proteins and Proteomics
Volume1600
Issue number1-2
DOIs
StatePublished - Nov 4 2002

Keywords

  • Calcium
  • Calmodulin
  • Death-associated protein kinase
  • Differentiation
  • Kinase inhibitor
  • Neuron
  • Perinatal cerebral hypoxia-ischemia
  • Stroke

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biophysics
  • Biochemistry
  • Molecular Biology

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