Cellular damage to lipids, proteins, and nucleic acids by endogenously generated peroxynitrite is associated with a number of neurological diseases. Results of earlier studies in this laboratory demonstrated that the ability of peroxynitrite to damage proteins is strongly dependent upon the hydrogen ion concentration and physiological levels of carbon dioxide and that it probably does not contribute significantly to formation of protein carbonyl derivatives or to the oxidation of methionine residues, both of which are widely used markers of oxidative protein damage. In continuing studies to identify major targets for peroxynitrite-dependent modification of proteins, the ability of peroxynitrite to nitrate tyrosine residues in bovine serum albumin (BSA) and glutamine synthetase (GS) was determined. Although these two proteins contain nearly identical numbers of tyrosine residues per subunit, they exhibit markedly different pH-dependent profiles of peroxynitrite-dependent nitration. It is thus evident that nitration of protein tyrosine residues is strongly dependent upon the molecular distribution of tyrosine residues and protein conformation. - peroxynitrite, protein carbonyls, peroxynitrite-carbon dioxide adducts

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Intramural Research (Z01)
Project #
1Z01HL000211-26
Application #
6290352
Study Section
Special Emphasis Panel (LB)
Project Start
Project End
Budget Start
Budget End
Support Year
26
Fiscal Year
1999
Total Cost
Indirect Cost
Name
National Heart, Lung, and Blood Institute
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Noda, Yasuko; Berlett, Barbara S; Stadtman, Earl R et al. (2007) Identification of enzymes and regulatory proteins in Escherichia coli that are oxidized under nitrogen, carbon, or phosphate starvation. Proc Natl Acad Sci U S A 104:18456-60
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Khan, Mohammed A S; Chock, P Boon; Stadtman, Earl R (2005) Knockout of caspase-like gene, YCA1, abrogates apoptosis and elevates oxidized proteins in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 102:17326-31
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Stadtman, Earl R; Arai, Hirofumi; Berlett, Barbara S (2005) Protein oxidation by the cytochrome P450 mixed-function oxidation system. Biochem Biophys Res Commun 338:432-6
Oubrahim, Hammou; Wang, Jun; Stadtman, Earl R et al. (2005) Molecular cloning and characterization of murine caspase-12 gene promoter. Proc Natl Acad Sci U S A 102:2322-7
Arai, Hirofumi; Berlett, Barbara S; Chock, P Boon et al. (2005) Effect of bicarbonate on iron-mediated oxidation of low-density lipoprotein. Proc Natl Acad Sci U S A 102:10472-7
Williams, W M; Stadtman, E R; Moskovitz, J (2004) Ageing and exposure to oxidative stress in vivo differentially affect cellular levels of PrP in mouse cerebral microvessels and brain parenchyma. Neuropathol Appl Neurobiol 30:161-8

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