Journal
TOXICOLOGY LETTERS
Volume 139, Issue 2-3, Pages 107-110Publisher
ELSEVIER SCI IRELAND LTD
DOI: 10.1016/S0378-4274(02)00424-1
Keywords
nitrogen monoxide/superoxide system; peroxynitrite; calcineurin
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The concept of NO as a redoxactive messenger has to be broadened by including superoxide as an antagonistic messenger. Superoxide alone was found to inhibit calcineurin by interacting with the FeII-ZnII binuclear site. This links oxidative stress conditions with a Ca-dependent phosphorylation/dephosphorylation cascade. When NO and superoxide are generated at equal fluxes the resulting peroxynitrite can cause tyrosine nitrations (e.g. prostacyclin synthase inhibition) or oxidations of zinc-fingers in proteins, indicating a new messenger function. Finally, if generated in excess, NO can convert peroxynitrite to N2O3 as a nitrosating agent. Thus, the NO/superoxide system provides four different messengers affecting important regulatory pathways. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.
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