Tempol diverts peroxynitrite/carbon dioxide reactivity toward albumin and cells from protein-tyrosine nitration to protein-cysteine nitrosation |
| |
| Authors: | Fernandes Denise C Medinas Danilo B Alves Maria Júlia M Augusto Ohara |
| |
| Institution: | 1. Institute for Genome Stability in Ageing and Disease, Medical Faculty, University of Cologne, 50931 Cologne, Germany;2. Cologne Excellence Cluster for Cellular Stress Responses in Ageing-Associated Diseases (CECAD) Research Center and Systems Biology of Ageing Cologne, University of Cologne, Joseph-Stelzmann-Str. 26, 50931 Cologne, Germany;3. Institute for Genetics, University of Cologne, Zülpicher Str. 47a, 50674 Cologne, Germany;1. Eli Lilly and Company, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA;2. Array BioPharma Inc., Boulder, CO, USA;1. Department of Biological Sciences, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea;2. Korea Institute of Toxicology, Daejeon 305-343, Republic of Korea;1. Max Planck Institute of Psychiatry, Munich, Germany;2. Department of Psychiatry and Psychotherapy, Ludwig-Maximilians-University Munich, Munich, Germany;3. Laboratory of Neuroproteomics, Department of Biochemistry, Institute of Biology, State University of Campinas (UNICAMP), Campinas, Sao Paulo, Brazil;1. School of Environmental Science and Engineering, Nanjing University of Information Science & Technology, Nanjing 210044, PR China;2. Collaborative Innovation Center of Atmospheric Environment and Equipment Technology, Nanjing University of Information Science & Technology, Nanjing 210044, PR China |
| |
| Abstract: | Tempol has been shown to protect experimental animals from injuries associated with excessive nitric oxide production. In parallel, tempol decreased the levels of protein-3-nitrotyrosine in the injured tissues, suggesting that it interacted with nitric oxide-derived oxidants such as nitrogen dioxide and peroxynitrite. Relevantly, a few recent studies have shown that tempol catalytically diverts peroxynitrite/carbon dioxide reactivity toward phenol from nitration to nitrosation. To examine whether this shift occurs in biological environments, we studied the effects of tempol (10-100 microM) on peroxynitrite/carbon dioxide (1 mM/2 mM) reactivity toward proteins, native bovine serum albumin (BSA) (0.5-0.7 cys/mol) and reductively denatured BSA (7-19 cys/mol), and cells (J774 macrophages). Although not a true catalyst, tempol strongly inhibited protein-tyrosine nitration (70-90%) and protein-cysteine oxidation (20-50%) caused by peroxynitrite/carbon dioxide in BSA, denatured BSA, and cells while increasing protein-cysteine nitrosation (200-400%). Tempol consumption was attributed mainly to its reaction with protein-cysteinyl radicals. Most of the tempol, however, reacted with the radicals produced from peroxynitrite/carbon dioxide, that is, nitrogen dioxide and carbonate radical anion. Accordingly, tempol decreased the yields of BSA-cysteinyl and BSA-tyrosyl/tryptophanyl radicals, as well their decay products such as protein-3-nitrotyrosine. The parallel increase in protein-nitrosocysteine yields demonstrated that part of the peroxynitrite is oxidized to nitric oxide by the oxammonium cation produced from tempol oxidation by peroxynitrite/carbon dioxide-derived radicals. Protein-nitrosocysteine formation was shown to occur by radical and nonradical mechanisms in studies with a protein-cysteinyl radical trapper. These studies may contribute to the understanding of the protective effects of tempol in animal models of inflammation. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ |
|
