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Relationship between protein nitration and oxidation and development of hyperoxic seizures.

Abstract
Recent studies have implicated nitric oxide (NO*) as a mediator of CNS hyperbaric O2 (HBO2) toxicity. One mechanism by which NO* may contribute to HBO2-induced brain toxicity involves a neurotoxic, pro-oxidative action of NO* via the formation of the potent oxidant peroxynitrite (ONOO-). The present study compares: (a) the formation of protein nitrotyrosine as a marker of ONOO- accumulation and (b) protein oxidation as an indicator of reactive oxygen species production during HBO2 exposure. Rats were exposed to 5 atm 100% O2 to pre-convulsive exposure or until the occurrence of electroencephalographic (EEG) seizures. After exposures, brains were analyzed for protein nitrotyrosine (NT) and protein carbonyl measurement by Western blot and for superoxide dismutase (SOD) activity by NBT assay. The results show a significant increase in protein NT, exceeding control level by several fold. There was only a slow and non-significant increase in the quantity of oxidized proteins during the pre-convulsive phase of HBO2 exposure. Levels of both protein NT and protein carbonyls were significantly (p<0.05) elevated after seizures. Total SOD activity was not changed during preconvulsive exposures, but was significantly (p<0.05) elevated post-seizures. The specific neuronal nitric oxide synthase (NOS) inhibitor, 7-nitroindazole (7-NI), significantly reduced the increases in seizure-induced protein NT and protein carbonyl and at the same time very effectively (p<0.05) delayed onset of HBO2 seizures. Pre-seizure increases in protein NT might indicate its role in the mechanism of HBO2-induced brain toxicity. This is supported by the observed capacity of 7-NI to inhibit tyrosine nitration and increase time to seizure.
AuthorsMikulas Chavko, Charles R Auker, Richard M McCarron
JournalNitric oxide : biology and chemistry (Nitric Oxide) Vol. 9 Issue 1 Pg. 18-23 (Aug 2003) ISSN: 1089-8603 [Print] United States
PMID14559428 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Enzyme Inhibitors
  • Indazoles
  • Proteins
  • Reactive Oxygen Species
  • Peroxynitrous Acid
  • Nitric Oxide
  • 3-nitrotyrosine
  • Tyrosine
  • Nitric Oxide Synthase
  • Superoxide Dismutase
  • Oxygen
  • 7-nitroindazole
Topics
  • Animals
  • Brain (metabolism)
  • Brain Chemistry
  • Electroencephalography
  • Enzyme Inhibitors (pharmacology)
  • Hyperbaric Oxygenation (adverse effects)
  • Indazoles (pharmacology)
  • Male
  • Nitric Oxide (metabolism)
  • Nitric Oxide Synthase (antagonists & inhibitors)
  • Oxidation-Reduction
  • Oxygen (administration & dosage)
  • Peroxynitrous Acid (analysis, biosynthesis)
  • Proteins (chemistry, metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species (analysis, metabolism)
  • Seizures (etiology, prevention & control)
  • Superoxide Dismutase (analysis, metabolism)
  • Time Factors
  • Tyrosine (analogs & derivatives, analysis)

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