4.3 Article

Characterization of UPF peptides, members of the glutathione analogues library, on the basis of their effects on oxidative stress-related enzymes

Journal

FREE RADICAL RESEARCH
Volume 43, Issue 6, Pages 572-580

Publisher

TAYLOR & FRANCIS LTD
DOI: 10.1080/10715760902918691

Keywords

Glutathione; glutathione analogues; glutathione peroxidase; glutathione reductase; MnSOD; NAD(P)H oxidase; oxidative stress

Funding

  1. Estonian Science Foundation [6503, 6574, 6588, 7856]
  2. University of Tartu
  3. Ministry of Education and Science of Estonia [SF0180105s08]
  4. European Union
  5. European Regional Development Fund

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Previously the authors have designed and synthesized a library of antioxidative glutathione analogues called UPF peptides which are superior to glutathione in hydroxyl radical elimination. This paper is a follow-up study which investigated the effects of the most promising members of the library (UPF1 and UPF17) on oxidative stress-related enzymes. At concentrations used in vivo experiments neither UPF peptide influenced the activity of glutathione peroxidase (GPx) when purified enzyme or erythrocyte lysate was used. At higher concentrations they inhibited GPx activity. UPF peptides had no effect on glutathione reductase (GR) activity. Also they, as well as glutathione itself, slightly increased MnSOD activity in human brain mitochondria and inhibited oxidative burst caused by neutrophil NAD(P) H oxidase. RT-PCR measurements showed that UPF1 and UPF17 have no effect on GPx and MnSOD expression level in human blood mononuclear cells. The results of this study confirm that investigated UPF peptides do not interfere with the enzymatic mechanisms of antioxidative defence and can be used as themselves or as a lead for the protector molecule design against excessive oxidative stress.

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