Hydrogen peroxide signaling via its transformation to a stereospecific alkyl hydroperoxide that escapes reductive inactivation.

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 1α. 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 whi

SUBMITTER: Queiroz RF 

PROVIDER: S-EPMC8595612 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature