Superoxide as inhibitor of calcineurin and mediator of redox regulation

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.