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 N(2)O(3) as a nitrosating agent. Thus, the NO/superoxide system provides four different messengers affecting important regulatory pathways.
Ullrich
Volker
V
Mathematisch-Naturwissenschaftliche Sektion, Fachbereich Biologie, Universität Konstanz, D-78457 Konstanz, Germany. volker.ullrich@uni-konstanz.de
Namgaladze
Dmitry
D
Frein
Daniel
D
D000818:Animals; D065095:Calcineurin Inhibitors; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D030421:Peroxynitrous Acid / Q000378:metabolism; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism*
D065095:Calcineurin Inhibitors; D013481:Superoxides; D030421:Peroxynitrous Acid; D009569:Nitric Oxide