Abstract

This proposal focuses on the effects of peroxynitrite on neutrophil functions. Based on the observations by these investigators that peroxynitrite could serve a as priming agent for neutrophil functions, and that this effect may be mediated primarily by nitration of tryrosine residues on neutrophil proteins, they propose that neutrophil function is modulated during inflammation or other periods of oxidant stress by tyrosine nitration on specific neutrophil proteins. To investigate this hypothesis, they propose to 1) analyze the effects of peroxynitrite-mediated tyrosine nitration on neutrophil functional responses such as calcium flux, rolling, adhesion, chemotaxis, degranulation, phagocytosis, and cytoine production; 2) analyze the effects of peroxynitrite treatment of purified NADPH oxidase proteins on oxidase assembly and enzymatic activity in vitro; 3) identify neutrophil proteins that are modified by tyrosine nitration in intact cells by immunoprecipitation, Western blotting, and amino acid sequencing; and 4) map specific sites of nitration on neutrophil proteins using mass spectrometry, peptide mapping, and amino acid sequencing.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL066575-02
Application #
6391243
Study Section
Hematology Subcommittee 2 (HEM)
Program Officer
Peterson, Charles M
Project Start
2000-09-30
Project End
2004-08-31
Budget Start
2001-09-01
Budget End
2002-08-31
Support Year
2
Fiscal Year
2001
Total Cost
$280,000
Indirect Cost

  Institution

Name
Montana State University Bozeman
Department
Veterinary Sciences
Type
Schools of Earth Sciences/Natur
DUNS #
City
Bozeman
State
MT
Country
United States
Zip Code
59717

  Publications

Yang, Xiaoping; Doser, Thomas A; Fang, Cindy X et al. (2006) Metallothionein prolongs survival and antagonizes senescence-associated cardiomyocyte diastolic dysfunction: role of oxidative stress. FASEB J 20:1024-6
Gauss, Katherine A; Bunger, Peggy L; Crawford, Matthew A et al. (2006) Variants of the 5'-untranslated region of human NCF2: expression and translational efficiency. Gene 366:169-79
Gauss, Katherine A; Bunger, Peggy L; Larson, Trina C et al. (2005) Identification of a novel tumor necrosis factor alpha-responsive region in the NCF2 promoter. J Leukoc Biol 77:267-78
Bhatti, Faizah; Mankhey, Richard W; Asico, Laureano et al. (2005) Mechanisms of antioxidant and pro-oxidant effects of alpha-lipoic acid in the diabetic and nondiabetic kidney. Kidney Int 67:1371-80
Quinn, Mark T; Gauss, Katherine A (2004) Structure and regulation of the neutrophil respiratory burst oxidase: comparison with nonphagocyte oxidases. J Leukoc Biol 76:760-81
Swain, Steve D; Siemsen, Daniel W; Nelson, Laura K et al. (2003) Inhibition of the neutrophil NADPH oxidase by adenosine is associated with increased movement of flavocytochrome b between subcellular fractions. Inflammation 27:45-58
Privratsky, Jamie R; Wold, Loren E; Sowers, James R et al. (2003) AT1 blockade prevents glucose-induced cardiac dysfunction in ventricular myocytes: role of the AT1 receptor and NADPH oxidase. Hypertension 42:206-12
Clements, Mark K; Siemsen, Daniel W; Swain, Steve D et al. (2003) Inhibition of actin polymerization by peroxynitrite modulates neutrophil functional responses. J Leukoc Biol 73:344-55
Puceat, Michel; Travo, Pierre; Quinn, Mark T et al. (2003) A dual role of the GTPase Rac in cardiac differentiation of stem cells. Mol Biol Cell 14:2781-92
Brar, Sukhdev S; Corbin, Zachary; Kennedy, Thomas P et al. (2003) NOX5 NAD(P)H oxidase regulates growth and apoptosis in DU 145 prostate cancer cells. Am J Physiol Cell Physiol 285:C353-69

Showing the most recent 10 out of 19 publications