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

Raphael F. Queiroz, Christopher P. Stanley, Kathryn Wolhuter, Stephanie M. Y. Kong, Ragul Rajivan, Naomi McKinnon, Giang T. H. Nguyen, Antonella Roveri, Sebastian Guttzeit, Philip Eaton, William A. Donald, Fulvio Ursini, Christine C. Winterbourn, Anita Ayer () and Roland Stocker ()
Additional contact information
Raphael F. Queiroz: Southwest Bahia State University
Christopher P. Stanley: Victor Chang Cardiac Research Institute
Kathryn Wolhuter: Victor Chang Cardiac Research Institute
Stephanie M. Y. Kong: The University of Sydney
Ragul Rajivan: Victor Chang Cardiac Research Institute
Naomi McKinnon: Victor Chang Cardiac Research Institute
Giang T. H. Nguyen: University of New South Wales
Antonella Roveri: University of Padova
Sebastian Guttzeit: St Thomas’ Hospital
Philip Eaton: Queen Mary University of London
William A. Donald: University of New South Wales
Fulvio Ursini: University of Padova
Christine C. Winterbourn: University of Otago Christchurch
Anita Ayer: Victor Chang Cardiac Research Institute
Roland Stocker: Victor Chang Cardiac Research Institute

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: 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 while it reacts more readily with its target, protein kinase G 1α. 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.

Date: 2021
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-26991-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-26991-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-26991-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().