Characterization of UPF peptides, members of the glutathione analogues library, on the basis of their effects on oxidative stress-related enzymes.
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.
Ehrlich
Kersti
K
Department of Biochemistry, Faculty of Medicine, University of Tartu, The Centre of Excellence of Translational Medicine, Tartu, Estonia. kersti.ehrlich@ut.ee
Ida
Katrin
K
Mahlapuu
Riina
R
Kairane
Ceslava
C
Oit
Ingrid
I
Zilmer
Mihkel
M
Soomets
Ursel
U
D000975:Antioxidants / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000201:enzymology; D005609:Free Radicals / Q000378:metabolism; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D005980:Glutathione Reductase / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D019151:Peptide Library; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013482:Superoxide Dismutase / Q000187:drug effects / Q000378:metabolism
C529051:4-methoxy-1-tyrosyl-gamma-glutamyl-cysteinyl-glycine; D000975:Antioxidants; D005609:Free Radicals; D019151:Peptide Library; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D019255:NADPH Oxidases; D005980:Glutathione Reductase; D005978:Glutathione