Skip to main content

Peroxynitrite formation and decreased catalase activity in autoimmune MRL-lpr/lpr mice.

Publication ,  Journal Article
Keng, T; Privalle, CT; Gilkeson, GS; Weinberg, JB
Published in: Mol Med
September 2000

BACKGROUND: (MRL)-lpr/lpr mice spontaneously develop autoimmune disease characterized by arthritis and glomerulonephritis. Nitric oxide is postulated to play a role in the disease pathogenesis, as mice treated with the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine (NMMA) show markedly reduced manifestations of the disease. The purpose of this study was to examine the role of peroxynitrite in disease development in MRL-lpr/lpr mice. MATERIALS AND METHODS: We examined kidney extracts from control and MRL-lpr/lpr mice for nitrotyrosine by immunoblot with a rabbit polyclonal anti-nitrotyrosine antibody. Catalase activity was determined spectrophotometrically or by activity staining of native polyacrylamide gels. In some experiments, we studied the ability of peroxynitrite and other agents to modify purified catalase in vitro. RESULTS: Kidney extracts from diseased mice had elevated levels of nitrotyrosine, and decreased levels of catalase activity and protein, relative to control mice. MRL-lpr/lpr mice treated with NMMA in vivo had decreased levels of nitrotyrosine, and demonstrated a partial restoration of both catalase activity and protein levels. Treatment of catalase in vitro with peroxynitrite or tetranitromethane at pH 8.0 resulted in protein nitration and a decrease in catalase activity. 1,3-morpholinosydnonimine (SIN-1), a peroxynitrite generator, also decreased the activity of catalase. CONCLUSIONS: These observations suggest that peroxynitrite formation, with an associated decrease in catalase activity and general decrease in antioxidant enzyme activity, may result in increased levels of hydrogen peroxide and other oxidants that can contribute to the pathogenesis of disease in MRL-lpr/lpr mice.

Duke Scholars

Published In

Mol Med

ISSN

1076-1551

Publication Date

September 2000

Volume

6

Issue

9

Start / End Page

779 / 792

Location

England

Related Subject Headings

  • omega-N-Methylarginine
  • Superoxide Dismutase
  • Reactive Oxygen Species
  • Oxidative Stress
  • Nitric Oxide Donors
  • Nitrates
  • Molsidomine
  • Mice, Knockout
  • Mice, Inbred MRL lpr
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Keng, T., Privalle, C. T., Gilkeson, G. S., & Weinberg, J. B. (2000). Peroxynitrite formation and decreased catalase activity in autoimmune MRL-lpr/lpr mice. Mol Med, 6(9), 779–792.
Keng, T., C. T. Privalle, G. S. Gilkeson, and J. B. Weinberg. “Peroxynitrite formation and decreased catalase activity in autoimmune MRL-lpr/lpr mice.Mol Med 6, no. 9 (September 2000): 779–92.
Keng T, Privalle CT, Gilkeson GS, Weinberg JB. Peroxynitrite formation and decreased catalase activity in autoimmune MRL-lpr/lpr mice. Mol Med. 2000 Sep;6(9):779–92.
Keng, T., et al. “Peroxynitrite formation and decreased catalase activity in autoimmune MRL-lpr/lpr mice.Mol Med, vol. 6, no. 9, Sept. 2000, pp. 779–92.
Keng T, Privalle CT, Gilkeson GS, Weinberg JB. Peroxynitrite formation and decreased catalase activity in autoimmune MRL-lpr/lpr mice. Mol Med. 2000 Sep;6(9):779–792.

Published In

Mol Med

ISSN

1076-1551

Publication Date

September 2000

Volume

6

Issue

9

Start / End Page

779 / 792

Location

England

Related Subject Headings

  • omega-N-Methylarginine
  • Superoxide Dismutase
  • Reactive Oxygen Species
  • Oxidative Stress
  • Nitric Oxide Donors
  • Nitrates
  • Molsidomine
  • Mice, Knockout
  • Mice, Inbred MRL lpr
  • Mice