Nitration of the Striatal Na,K-ATPase α3 Isoform Occurs in Normal Brain Development but Is Not Increased during Hypoxia-Ischemia in Newborn Piglets

W. Christopher Golden, Ansgar M. Brambrink, Richard J. Traystman, Donald H. Shaffner, Lee J. Martin

Research output: Contribution to journalArticlepeer-review

13 Scopus citations


Neonatal hypoxia-ischemia (HI) can result in significant sensorimotor abnormalities, including movement and posture disorders. These neurological impairments are believed to result from basal ganglia (striatum) damage, but the exact cause of this injury is not known. One mechanism involved in brain injury after HI is the generation of reactive oxygen species, which damage cellular macromolecules. We tested the hypothesis that inactivation of plasma membrane enzyme Na,K-ATPase during striatal neurodegeneration after HI emerges with peroxynitrite attack on the enzyme. In vitro, reaction of peroxynitrite (100-500 μM) with purified Na,K-ATPase produced nitration of the α (catalytic) and β (transport) subunits, as quantified by immunoblots of the reaction products for nitrotyrosine. To evaluate for peroxynitrite damage to Na,K-ATPase in vivo, striatal plasma membrane fractions from 1-week-old piglets subjected to asphyxic cardiac arrest and recovery were also studied by immunoprecipitation. During the progression of striatal neurodegeneration and loss of enzyme function 3-24 h after arrest, nitration of the α 3 (neuronal) isoform of Na,K-ATPase was not increased relative to sham control. Suprisingly, however, nitration of this α isoform occurs during normal brain development and peaks at 2 weeks of age. We conclude that Na,K-ATPase is a target of peroxynitrite, but that this mechanism is not responsible for enzyme inactivation after HI. Protein nitration may serve as marker of other normal, noninjurious cell processes in the developing brain.

Original languageEnglish (US)
Pages (from-to)1883-1889
Number of pages7
JournalNeurochemical Research
Issue number12
StatePublished - Dec 2003


  • Cell death
  • Newborn brain damage
  • Protein nitration
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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