Decrease of Brain Protein Kinase C, Protein Kinase A, and Cyclin-Dependent Kinase Correlating with pH Precedes Neuronal Death in Neonatal Asphyxia

Barbara Lubec, Elisabetta Dell'Anna, Susanne Fang-Kircher, Manfred Marx, Mario Herrera-Marschitz, Gert Lubec

Research output: Contribution to journalArticle

Abstract

Background: Acidosis, energy depletion, overstimulation by excitatory amino acids, and free radical-mediated reactions are the major, current concepts for the explanation of damage and death resulting from asphyxia. Impaired protein phosphorylation by protein kinase C represents another mechanism incriminated in cell death. Methods: We used a nonsophisticated perinatal asphyxia model to study brain (frontal cortex) pH, ATP, protein kinases PKC, PKA, and cyclin-dependent kinase. We used o-tyrosine, a marker for hydroxyl radical attack, and LPO 586, a spectrophotometric assay, to study lipid peroxidation products. The antioxidant enzymes catalase, superoxide dismutase, and glutathione peroxidase were used in the frontal cortex. In addition, a cell death ELISA and histology to evaluate cell death were performed. Results: Brain pH and protein kinases were decreasing with the length of the asphyctic periods, and energy depletion was shown by a drop of ATP levels, whereas no evidence for the involvement of free radical-mediated mechanisms was obtained. Cell death was shown by the cell death ELISA as early as 10 minutes after the asphyctic period, and histologically, cell death could be revealed but not before day 8 after asphyxia. Conclusion: Acidosis and/or impaired protein kinases, but not free radical mechanisms, may play a role in the pathobiochemistry of cell death in neonatal asphyxia of the rat.

Original languageEnglish
Pages (from-to)284-294
Number of pages11
JournalJournal of Investigative Medicine
Volume45
Issue number5
Publication statusPublished - Jun 1997

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Keywords

  • Active oxygen species
  • Antioxidant enzymes
  • Asphyxia
  • ATP
  • Neonatal
  • Neuron
  • Protein kinase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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