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Enzyme
Compound
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Query: EC:1.17.3.2 (
xanthine oxidase
)
8,383
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The conditions under which nitric oxide (.NO) may modulate or promote lung injury have not been identified. We hypothesized that .NO-induced injury results from peroxynitrite, formed by the reaction of .NO with superoxide. The simultaneous generation of .NO and superoxide by 3-morpholinosydnonimine (SIN-1, 0.1-2 mM) resulted in oxidation of dihydrorhodamine, a marker of peroxynitrite production, and a dose-dependent decrease in the ability of
SP-A
to enhance lipid aggregation. Western blot analysis of SIN-1 exposed
SP-A
samples, overlaid with a polyclonal antibody against nitrotyrosine, were consistent with nitration of
SP-A
tyrosine residues. Superoxide dismutase (100 U/ml), L-cysteine (5 mM),
xanthine oxidase
(10 mU/ml) and xanthine (500 microM), or urate (100 microM) prevented the SIN-1-induced dihydrorhodamine oxidation and injury to
SP-A
. .NO alone, generated by S-nitroso-N-acetylpenicillamine plus 100 microM L-cysteine, or superoxide and hydrogen peroxide, generated by pterin and
xanthine oxidase
in the absence of iron, did not damage
SP-A
or oxidize dihydrorhodamine. We concluded that peroxynitrite, but not .NO or superoxide and hydrogen peroxide, in concentrations likely to be encountered in vivo, caused nitrotyrosine formation and decreased the ability of
SP-A
to aggregate lipids.
...
PMID:Concurrent generation of nitric oxide and superoxide damages surfactant protein A. 794 50
Nitric oxide (.NO) is a signal transducing free radical which can modify oxidant stress by limiting superoxide (O2.-)-mediated injury. However, the product of .NO reaction with O2.-, peroxynitrite (ONOO-), is a potent oxidizing and nitrating agent. Exposure of a mixture containing phosphatidylcholine liposomes and surfactant apoprotein A (
SP-A
; 10% by weight) to increasing concentrations of .NO, generated by spermine NONOate, and constant O2.- levels, produced by the action of
xanthine oxidase
on lumazine, suppressed O2.(-)-induced lipid peroxidation in the presence of Fe3(+)- EDTA. On the other hand, an increase in the .NO/O2.- value resulted in nitration of
SP-A
tyrosine residues, located in the carbohydrate recognition domain (CRD), and decreased the ability of
SP-A
to aggregate lipids and bind mannose, two functions that require an intact CRD.
SP-A
was also nitrated to a large extent following exposure to 3-morpholinosydnonimine (SIN-1) or tetranitromethane at pH 8. In each case, increased nitrotyrosine content correlated in a monotonic fashion with inhibition of lipid aggregation and mannose binding, correlated with the extent of functional inhibition. Superoxide dismutase (2400 U/ml) and urate (100 microM; nonspecific scavenger of both ONOO- and hydroxyl radical), but not mannitol (50 mM; hydroxyl radical scavenger), prevented the SIN-1-induced injury to
SP-A
. In contrast, spermine NON-Oate or
xanthine oxidase
plus lumazine alone neither inhibited
SP-A
function nor nitrated the protein. These results indicate that at high concentrations, .NO inhibit O2.-induced lipid peroxidation. However, ONOO., formed by the reaction of .NO and O2.-, nitrates
SP-A
leading to decreased ability to aggregate lipids and bind mannose.
...
PMID:Nitration of surfactant protein A (SP-A) tyrosine residues results in decreased mannose binding ability. 880 82
