The thioredoxin and glutaredoxin systems are efficient electron donors to human plasma glutathione peroxidase

Research output: Contribution to journalArticle

Abstract

Human plasma glutathione peroxidase (GSH-Px) is a distinct extracellular selenoenzyme that detoxifies hydroperoxides when used with GSH in high (mM) non-physiological concentrations. We have discovered that NADPH and human thioredoxin reductase (TR) by itself or with thioredoxin (Trx) are efficient electron donors to this human plasma peroxidase. Incubation of 0.05 microM TR with 0.25 microM GSH-Px, in a system free from GSH, resulted in reduction of t-butyl hydroperoxide. Addition of Trx, 2.5 and 5 microM, respectively, further increased the rate of the reaction. These data were obtained using an assay measuring the oxidation of NADPH. A direct assay demonstrated the formation of cumyl alcohol from cumene hydroperoxide in this GSH-independent peroxidase reaction. Incubation of 0.25 microM GSH-Px with a low concentration of GSH (10 microM), representing the upper level in plasma, plus excess glutathione reductase and NADPH did not result in any reduction of t-butyl hydroperoxide. However, after addition of 2.5 microM human glutaredoxin, a linear peroxidase reaction started. The results suggest that extracellular TR, Trx, or glutaredoxin are reductants for the selenium-dependent peroxidase rather than GSH.

Details

Authors
Organisations
External organisations
  • Karolinska Institutet
  • Lund University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Biological Sciences
Original languageEnglish
Pages (from-to)29382-29384
Number of pages3
JournalJournal of Biological Chemistry
Volume269
Issue number47
Publication statusPublished - 1994
Publication categoryResearch
Peer-reviewedYes