Publikation: Autocatalytic tyrosine nitration of prostaglandin endoperoxide synthase-2 in LPS-stimulated RAW 264.7 macrophages
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In the literature, biological tyrosine nitrations have been reported to depend not only on peroxynitrite but also on nitrite/hydrogen peroxide linked to catalysis by myeloperoxidase. In endotoxin-stimulated RAW 264.7 macrophages, we have detected a major nitrotyrosine positive protein band around 72 kDa and identified it as prostaglandin endoperoxide synthase-2 (PGHS-2). Isolated PGHS-2 in absence of its substrate arachidonate was not only tyrosine-nitrated with peroxynitrite, but also with nitrite/hydrogen peroxide in complete absence of myeloperoxidase. Our data favor an autocatalytic activation of nitrite by PGHS-2 with a subsequent nitration of the essential tyrosine residue in the cyclooxygenase domain. Under inflammatory conditions, nitrite formed via NO-synthase-2 may therefore act as an endogenous regulator for PGHS-2 in stimulated macrophages. Nitration of PGHS-2 by the autocatalytic activation of nitrite further depends on the intracellular concentration of arachidonate since arachidonate reacted competitively with nitrite and could prevent PGHS-2 from nitration when excessively present.
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SCHILDKNECHT, Stefan, Kathrin HEINZ, Andreas DAIBER, Jürg HAMACHER, Cengiz KAVAKLÍ, Volker ULLRICH, Markus BACHSCHMID, 2006. Autocatalytic tyrosine nitration of prostaglandin endoperoxide synthase-2 in LPS-stimulated RAW 264.7 macrophages. In: Biochemical and Biophysical Research Communications. 2006, 340(1), pp. 318-325. ISSN 0006-291X. eISSN 1090-2104. Available under: doi: 10.1016/j.bbrc.2005.12.009BibTex
@article{Schildknecht2006-02-03Autoc-38920, year={2006}, doi={10.1016/j.bbrc.2005.12.009}, title={Autocatalytic tyrosine nitration of prostaglandin endoperoxide synthase-2 in LPS-stimulated RAW 264.7 macrophages}, number={1}, volume={340}, issn={0006-291X}, journal={Biochemical and Biophysical Research Communications}, pages={318--325}, author={Schildknecht, Stefan and Heinz, Kathrin and Daiber, Andreas and Hamacher, Jürg and Kavaklí, Cengiz and Ullrich, Volker and Bachschmid, Markus} }
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