Abstract
Involvement of peroxynitrite (ONOO-) in inflammatory diseases has been implicated by detection of 3-nitrotyrosine, an allegedly characteristic protein oxidation product, in various inflamed tissues. We show here that nitrite (NO2/-), the primary metabolic end product of nitric oxide (NO·), can he oxidized by the heme peroxidases horseradish peroxidase, myeloperoxidase (MPO), and lactoperoxidase (LPO), in the presence of hydrogen peroxide (H2O2), to most likely form NO2/·, which can also contribute to tyrosine nitration during inflammatory processes. Phenolic nitration by MPO- catalyzed NO2/- oxidation is only partially inhibited by chloride (Cl-), the presumed major physiological substrate for MPO. In fact, low concentrations of NO2/- (2-10 μM) catalyze MPO-mediated oxidation of Cl- , indicated by increased chlorination of monochlorodimedon or 4- hydroxyphenylacetic acid, most likely via reduction of MPO compound II. Peroxidase-catalyzed oxidation of NO2/-, as indicated by phenolic nitration, was also observed in the presence of thiocyanate (SCN-), an alternative physiological substrate for mammalian peroxidases. Collectively, our results suggest that NO2/-, at physiological or pathological levels, is a substrate for the mammalian peroxidases MPO and lactoperoxidase and that formation of NO2/· via peroxidase-catalyzed oxidation of NO2 - may provide an additional pathway contributing to cytotoxicity or host defense associated with increased NO· production.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 7617-7625 |
| Number of pages | 9 |
| Journal | Journal of Biological Chemistry |
| Volume | 272 |
| Issue number | 12 |
| DOIs | |
| State | Published - 1997 |
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ASJC Scopus subject areas
- Biochemistry
Cite this
Formation of reactive nitrogen species during peroxidase-catalyzed oxidation of nitrite : A potential additional mechanism of nitric oxide- dependent toxicity. / Van Der Vliet, Albert; Eiserich, Jason P.; Halliwell, Barry; Cross, Carroll E.
In: Journal of Biological Chemistry, Vol. 272, No. 12, 1997, p. 7617-7625.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Formation of reactive nitrogen species during peroxidase-catalyzed oxidation of nitrite
T2 - A potential additional mechanism of nitric oxide- dependent toxicity
AU - Van Der Vliet, Albert
AU - Eiserich, Jason P.
AU - Halliwell, Barry
AU - Cross, Carroll E
PY - 1997
Y1 - 1997
N2 - Involvement of peroxynitrite (ONOO-) in inflammatory diseases has been implicated by detection of 3-nitrotyrosine, an allegedly characteristic protein oxidation product, in various inflamed tissues. We show here that nitrite (NO2/-), the primary metabolic end product of nitric oxide (NO·), can he oxidized by the heme peroxidases horseradish peroxidase, myeloperoxidase (MPO), and lactoperoxidase (LPO), in the presence of hydrogen peroxide (H2O2), to most likely form NO2/·, which can also contribute to tyrosine nitration during inflammatory processes. Phenolic nitration by MPO- catalyzed NO2/- oxidation is only partially inhibited by chloride (Cl-), the presumed major physiological substrate for MPO. In fact, low concentrations of NO2/- (2-10 μM) catalyze MPO-mediated oxidation of Cl- , indicated by increased chlorination of monochlorodimedon or 4- hydroxyphenylacetic acid, most likely via reduction of MPO compound II. Peroxidase-catalyzed oxidation of NO2/-, as indicated by phenolic nitration, was also observed in the presence of thiocyanate (SCN-), an alternative physiological substrate for mammalian peroxidases. Collectively, our results suggest that NO2/-, at physiological or pathological levels, is a substrate for the mammalian peroxidases MPO and lactoperoxidase and that formation of NO2/· via peroxidase-catalyzed oxidation of NO2 - may provide an additional pathway contributing to cytotoxicity or host defense associated with increased NO· production.
AB - Involvement of peroxynitrite (ONOO-) in inflammatory diseases has been implicated by detection of 3-nitrotyrosine, an allegedly characteristic protein oxidation product, in various inflamed tissues. We show here that nitrite (NO2/-), the primary metabolic end product of nitric oxide (NO·), can he oxidized by the heme peroxidases horseradish peroxidase, myeloperoxidase (MPO), and lactoperoxidase (LPO), in the presence of hydrogen peroxide (H2O2), to most likely form NO2/·, which can also contribute to tyrosine nitration during inflammatory processes. Phenolic nitration by MPO- catalyzed NO2/- oxidation is only partially inhibited by chloride (Cl-), the presumed major physiological substrate for MPO. In fact, low concentrations of NO2/- (2-10 μM) catalyze MPO-mediated oxidation of Cl- , indicated by increased chlorination of monochlorodimedon or 4- hydroxyphenylacetic acid, most likely via reduction of MPO compound II. Peroxidase-catalyzed oxidation of NO2/-, as indicated by phenolic nitration, was also observed in the presence of thiocyanate (SCN-), an alternative physiological substrate for mammalian peroxidases. Collectively, our results suggest that NO2/-, at physiological or pathological levels, is a substrate for the mammalian peroxidases MPO and lactoperoxidase and that formation of NO2/· via peroxidase-catalyzed oxidation of NO2 - may provide an additional pathway contributing to cytotoxicity or host defense associated with increased NO· production.
UR - http://www.scopus.com/inward/record.url?scp=0030909465&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0030909465&partnerID=8YFLogxK
U2 - 10.1074/jbc.272.12.7617
DO - 10.1074/jbc.272.12.7617
M3 - Article
C2 - 9065416
AN - SCOPUS:0030909465
VL - 272
SP - 7617
EP - 7625
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 0021-9258
IS - 12
ER -