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Distinction between nitrosating mechanisms within human cells and aqueous solution.

Abstract
The quintessential nitrosating species produced during NO autoxidation is N(2)O(3). Nitrosation of amine, thiol, and hydroxyl residues can modulate critical cell functions. The biological mechanisms that control reactivity of nitrogen oxide species formed during autoxidation of nano- to micromolar levels of NO were examined using the synthetic donor NaEt(2)NN(O)NO (DEA/NO), human tumor cells, and 4,5-diaminofluorescein (DAF). Both the disappearance of NO and formation of nitrosated product from DAF in aerobic aqueous buffer followed second order processes; however, consumption of NO and nitrosation within intact cells were exponential. An optimal ratio of DEA/NO and 2-phenyl-4,4,5,5-tetramethylimidazole-1-oxyl 3-oxide (PTIO) was used to form N(2)O(3) through the intermediacy of NO(2). This route was found to be most reflective of the nitrosative mechanism within intact cells and was distinct from the process that occurred during autoxidation of NO in aqueous media. Manipulation of the endogenous scavengers ascorbate and glutathione indicated that the location, affinity, and concentration of these substances were key determinants in dictating nitrosative susceptibility of molecular targets. Taken together, these findings suggest that the functional effects of nitrosation may be organized to occur within discrete domains or compartments. Nitrosative stress may develop when scavengers are depleted and this architecture becomes compromised. Although NO(2) was not a component of aqueous NO autoxidation, the results suggest that the intermediacy of this species may be a significant factor in the advent of either nitrosation or oxidation chemistry in biological systems.
AuthorsM G Espey, K M Miranda, D D Thomas, D A Wink
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 276 Issue 32 Pg. 30085-91 (Aug 10 2001) ISSN: 0021-9258 [Print] United States
PMID11404354 (Publication Type: Journal Article)
Chemical References
  • 4,5-diaminofluorescein
  • Cyclic N-Oxides
  • Imidazoles
  • Indicators and Reagents
  • Nitrogen Oxides
  • Reactive Oxygen Species
  • 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide
  • Nitric Oxide
  • Glutathione
  • Ascorbic Acid
  • Oxygen
  • Fluorescein
Topics
  • Ascorbic Acid (metabolism)
  • Cyclic N-Oxides (pharmacology)
  • Fluorescein (pharmacology)
  • Glutathione (metabolism)
  • Humans
  • Imidazoles (pharmacology)
  • Indicators and Reagents (pharmacology)
  • Kinetics
  • Models, Chemical
  • Nitric Oxide (chemistry, metabolism)
  • Nitrogen Oxides (chemistry, metabolism, pharmacology)
  • Nitrosation
  • Oxygen (metabolism)
  • Protein Structure, Tertiary
  • Reactive Oxygen Species
  • Spectrometry, Fluorescence
  • Stress, Physiological
  • Time Factors
  • Tumor Cells, Cultured

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