Peroxynitrite signaling: receptor tyrosine kinases and activation of stress-responsive pathways.
Peroxynitrite, generated for example in inflammatory processes, is capable of nitrating and oxidizing biomolecules, implying a considerable impact on the integrity of cellular structures. Cells respond to stressful conditions by the activation of signaling pathways, including receptor tyrosine kinase-dependent pathways such as mitogen-activated protein kinases and the phosphoinositide-3-kinase/Akt pathway. Peroxynitrite affects signaling pathways by nitration as well as by oxidation: while nitration of tyrosine residues by peroxynitrite modulates signaling processes relying on tyrosine phosphorylation and dephosphorylation, oxidation of phosphotyrosine phosphatases may lead to an alteration in the tyrosine phosphorylation/dephosphorylation balance. The flavanol (-)-epicatechin is a potent inhibitor of tyrosine nitration and may be employed as a tool to distinguish signaling effects due to tyrosine nitration from those that are due to oxidation reactions.
Institut für Physiologische Chemie I, Heinrich-Heine-Universität Düsseldorf, Düsseldorf, Germany. larsoliver.klotz@uni-duesseldorf.de
Lars-Oliver
LO
Klotz
Peter
P
Schroeder
Helmut
H
Sies
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006801:Humans; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases; D008954:Models, Biological; D008956:Models, Chemical; D009584:Nitrogen / Q000378:metabolism*; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism; D030421:Peroxynitrous Acid / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D015398:Signal Transduction; D014158:Transcription, Genetic; D014443:Tyrosine / Q000378:metabolism*
D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D030421:Peroxynitrous Acid; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases; D009584:Nitrogen; D010100:Oxygen