Oxidation of 2-Cys-peroxiredoxins by Arachidonic Acid Peroxide Metabolites of Lipoxygenases and Cyclooxygenase-2

• Published in: The Journal of biological chemistry Vol. 282; no. 45; pp. 32623 - 32629
• Main Authors: Cordray, Pauline, Doyle, Kelly, Edes, Kornelia, Moos, Philip J., Fitzpatrick, Frank A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.11.2007; American Society for Biochemistry and Molecular Biology
• Subjects: Arachidonic Acid - metabolism; Catalysis; Cell Line; Cyclooxygenase 2 - metabolism; Cysteine - metabolism; Enzyme Activation - drug effects; Gene Expression Regulation, Enzymologic; Humans; Lipoxygenase - genetics; Lipoxygenase - metabolism; Lipoxygenase Inhibitors - pharmacology; Oxidation-Reduction; Peroxides - metabolism; Peroxiredoxins - metabolism; Protein Binding
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M704369200

Human peroxiredoxins serve dual roles as anti-oxidants and regulators of H2O2-mediated cell signaling. The functional versatility of peroxiredoxins depends on progressive oxidation of key cysteine residues. The sulfinic or sulfonic forms of peroxiredoxin lose their peroxidase activity, which allows cells to accumulate H2O2 for signaling or pathogenesis in inflammation, cancer, and other disorders. We report that arachidonic acid lipid hydroperoxide metabolites of 5-, 12-, 15-lipoxygenase-1, and cyclooxygenase-2 oxidize the 2-Cys-peroxiredoxins 1, 2, and 3 to their sulfinic and sulfonic forms. When added exogenously to cells, 5-, 12- and 15-hydroperoxy-eicosatetraenoic acids also over-oxidized peroxiredoxins. Our results suggest that lipoxygenases and cyclooxygenases may affect 2-Cys peroxiredoxin signaling, analogous to NADPH oxidases in the “floodgate” model (Wood, Z. A., Poole, L. B, and Karplus P. A. (2003) Science 300, 600–653). Peroxiredoxin-dependent mechanisms may modulate the receptor-dependent actions of autocoids derived from cellular lipoxygenase and cyclooxygenase catalysis.