Protection by selenoprotein P in human plasma against peroxynitrite-mediated oxidation and nitration.
In order to study functions of selenoprotein P in human plasma, its level was lowered via two techniques, chromatography on Sepharose-bound heparin, or immunoprecipitation; Western blot analysis showed that both techniques were effective at substantially lowering selenoprotein P levels in plasma. When peroxynitrite was infused to maintain a 0.9 microM steady-state concentration, plasma made deficient in selenoprotein P diminished benzoate hydroxylation significantly less than control plasma. Similar differences were found for protein 3-nitrotyrosine formation, determined by Western blot analysis. Conversely, in a selenoprotein P-enriched plasma preparation obtained via heparin-Sepharose chromatography, protection against benzoate hydroxylation was above controls. Likewise, a supernatant from control plasma that had been exposed to anti-selenoprotein P antibodies was less efficient in preventing oxidation and nitration reactions of peroxynitrite than the supernatant from plasma exposed to a non-specific antibody (rabbit anti-sheep IgG). These data demonstrate a role of selenoprotein P in human plasma in the defense against peroxynitrite.
Arteel
G E
GE
Institut für Physiologische Chemie I, Heinrich-Heine-Universität Düsseldorf, Germany.
Mostert
V
V
Oubrahim
H
H
Briviba
K
K
Abel
J
J
Sies
H
H
D015153:Blotting, Western; D006801:Humans; D009566:Nitrates / Q000378:metabolism*; D018384:Oxidative Stress; D011506:Proteins / Q000276:immunology / Q000378:metabolism*; D051149:Selenoprotein P; D051140:Selenoproteins; D014443:Tyrosine / Q000031:analogs & derivatives / Q000097:blood
D009566:Nitrates; D011506:Proteins; D051149:Selenoprotein P; D051140:Selenoproteins; C039642:peroxynitric acid; C002744:3-nitrotyrosine; D014443:Tyrosine