Autocatalytic tyrosine nitration of prostaglandin endoperoxide synthase-2 in LPS-stimulated RAW 264.7 macrophages


Schildknecht S., Heinz K., Daiber A., Hamacher J., KAVAKLI C. , Ullrich V., ...Daha Fazla

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, cilt.340, sa.1, ss.318-325, 2006 (SCI İndekslerine Giren Dergi) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 340 Konu: 1
  • Basım Tarihi: 2006
  • Doi Numarası: 10.1016/j.bbrc.2005.12.009
  • Dergi Adı: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
  • Sayfa Sayıları: ss.318-325

Özet

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 al\so 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. (c) 2005 Elsevier Inc. All rights reserved.