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Molecular Medicine

, Volume 16, Issue 9–10, pp 335–342 | Cite as

Peroxynitrite-induced Nitration of Cyclooxygenase-2 and Inducible Nitric Oxide Synthase Promotes Their Binding in Diabetic Angiopathy

  • Yanning Li
  • Jinsheng Qi
  • Kun Liu
  • Bin Li
  • Hui Wang
  • Jinhai Jia
Research Article

Abstract

Cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) play crucial roles in diabetic angiopathy. In vivo, however, the following facts remain unknown: whether COX-2 and iNOS bind, how peroxynitrite-induced nitration of COX-2 and iNOS affects their binding if they do bind and what effects of this mechanism contribute to diabetic angiopathy. This study focused on the issues above. Diabetes was induced in Wistar male rats by intraperitoneal injection of streptozotocin. As a specific scavenger of peroxynitrite, urate was used. After 13 wks of diabetes, the morphological and biochemical changes of the rats showed obvious diabetic angiopathy. There exists in vivo colocalization and binding of COX-2 and iNOS in diabetic angiopathy. The nitration level of total and coimmunoprecipitated COX-2 and iNOS increased significantly, and, simultaneously, their binding and activity increased in the diabetes group. In the diabetes + urate group, the nitration level of COX-2 and iNOS decreased and their binding reduced, consistent with their decreased activity and the attenuated pathological changes in the rat aorta and glomerulus. The results provide in vivo evidence that COX-2 and iNOS can bind in diabetic angiopathy and that peroxynitrite-induced nitration of COX-2 and iNOS promotes their binding, contributing to diabetic angiopathy.

Notes

Acknowledgments

This study was supported by the Hebei Natural Science Foundation (C2009001092), the Bureau of Education of Hebei province (B2004122), the Bureau of Science and Technology of Hebei province (07276101D), the Bureau of Science and Technology of Shijiazhuang city (04146173A and 07120803a), the Bureau of Sanitation of Hebei province (04062) and Hebei Medical University (040028).

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Copyright information

© The Feinstein Institute for Medical Research 2010

Authors and Affiliations

  • Yanning Li
    • 1
  • Jinsheng Qi
    • 2
  • Kun Liu
    • 2
  • Bin Li
    • 2
  • Hui Wang
    • 3
  • Jinhai Jia
    • 2
  1. 1.Department of Molecular BiologyHebei Key Lab of Laboratory AnimalShijiazhuang, PRChina
  2. 2.Department of BiochemistryHebei Medical UniversityShijiazhuangChina
  3. 3.Department of PathologyHebei Medical UniversityShijiazhuang, PRChina

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