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Tyrosine nitration in prostaglandin H(2) synthase
Ruba S Deeb1, Matthew J Resnick, Dev Mittar
1Center of Vascular Biology, Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10021, USA.
Journal of Lipid Research
|October 5, 2002
Summary
Nitrogen oxides (NO(x)) can nitrate prostaglandin H(2) synthase-1 (PGHS-1), reducing its activity. This study found nitrated PGHS-1 in human atherosclerotic tissue, suggesting NO(x) contributes to oxidative damage in atherosclerosis.
Area of Science:
- Biochemistry
- Molecular Biology
- Pathology
Background:
- Prostaglandin H(2) synthase-1 (PGHS-1) plays a crucial role in vascular function.
- Nitrogen oxides (NO(x)) are implicated in the pathogenesis of atherosclerosis.
- Tyrosine nitration is a marker of oxidative stress.
Purpose of the Study:
- To investigate the effects of various NO(x) species on PGHS-1 nitration.
- To assess the impact of NO(x)-induced nitration on PGHS-1 activity.
- To determine the presence of nitrated PGHS-1 in human atherosclerotic tissue.
Main Methods:
- Purified PGHS-1 and vascular smooth muscle cells were treated with different NO(x) species.
- Nitration extent was quantified using electrospray ionization mass spectrometry and UV/Vis spectroscopy.
- Human atheromatous tissue was analyzed for PGHS-1 nitration.
Main Results:
- Peroxynitrite and tetranitromethane induced tyrosine nitration of PGHS-1.
- Tetranitromethane was more potent than peroxynitrite and nitrogen dioxide in nitrating a tyrosine-containing peptide.
- Nitrated PGHS-1 was detected in human atherosclerotic tissue, and nitration inversely correlated with enzyme activity.
Conclusions:
- Specific NO(x) species, particularly peroxynitrite, can nitrate PGHS-1.
- PGHS-1 nitration leads to decreased enzyme activity.
- The presence of nitrated PGHS-1 in atherosclerotic lesions suggests a role for NO(x)-mediated oxidative damage in atherosclerosis.