Queiroz, Raphael F. and Stanley, Christopher P. and Wolhuter, Kathryn and Kong, Stephanie M. Y. and Rajivan, Ragul and McKinnon, Naomi and Nguyen, Giang T. H. and Roveri, Antonella and Guttzeit, Sebastian and Eaton, Philip and Donald, William A. and Ursini, Fulvio and Winterbourn, Christine C. and Ayer, Anita and Stocker, Roland (2021) Hydrogen peroxide signaling via its transformation to a stereospecific alkyl hydroperoxide that escapes reductive inactivation. Nature Communications, 12 (1). ISSN 2041-1723
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1229-Hydrogen-peroxide-signaling-via-its-transformation-to-a-stereospecific-alkyl-hydroperoxide-that-escapes-reductive-inactivation.pdf Available under License Creative Commons Attribution No Derivatives. Download (2MB) | Preview |
Abstract
During systemic inflammation, indoleamine 2,3-dioxygenase 1 (IDO1) becomes expressed in endothelial cells where it uses hydrogen peroxide (H2O2) to oxidize L-tryptophan to the tricyclic hydroperoxide, cis-WOOH, that then relaxes arteries via oxidation of protein kinase G 1alpha. Here we show that arterial glutathione peroxidases and peroxiredoxins that rapidly eliminate H2O2, have little impact on relaxation of IDO1-expressing arteries, and that purified IDO1 forms cis-WOOH in the presence of peroxiredoxin 2. cis-WOOH oxidizes protein thiols in a selective and stereospecific manner. Compared with its epimer trans-WOOH and H2O2, cis-WOOH reacts slower with the major arterial forms of glutathione peroxidases and peroxiredoxins while it reacts more readily with its target, protein kinase G 1alpha. Our results indicate a paradigm of redox signaling by H2O2 via its enzymatic conversion to an amino acid-derived hydroperoxide that 'escapes' effective reductive inactivation to engage in selective oxidative activation of key target proteins.
| Item Type: | Article |
|---|---|
| Subjects: | R Medicine > R Medicine (General) |
| Depositing User: | Repository Administrator |
| Date Deposited: | 03 Jun 2022 05:14 |
| Last Modified: | 09 Jun 2022 00:53 |
| URI: | http://eprints.victorchang.edu.au/id/eprint/1229 |
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