Nitric oxide inactivates xanthine dehydrogenase and xanthine oxidase in interferon-gamma-stimulated macrophages

American Journal of Respiratory Cell and Molecular Biology
J E RinaldoV L Shepherd

Abstract

Interferon-gamma (IFN-gamma) has been reported to up-regulate transcription of the xanthine dehydrogenase (XDH) gene and to regulate XDH and xanthine oxidase (XO) activity in endothelial cells and liver tissue. Macrophages are a source of XDH/XO activity at inflammatory sites and are functionally regulated by IFN-gamma. We studied the effect of IFN-gamma on XDH and XO in rat bone marrow macrophages, rat alveolar macrophages, and murine RAW cells. Instead of an induction of enzyme activity, XDH/XO activity was almost totally lost after incubation with 100 to 1,000 U/ml of IFN-gamma for 24 h in all three cell types. The loss of cell-associated XDH/XO activity was not correlated with the appearance of XDH/XO activity in the media. In addition, the loss of XDH/XO activity could not be accounted for by transcriptional repression, since there was an increase in steady-state levels of XDH mRNA. To determine whether XDH/XO activity might be lost through nitric oxide-mediated inactivation of XDH/XO, we compared the time course and dose response for XDH/XO inactivation with that of nitric oxide production and found them similar. Treatment with the nitric oxide inhibitor N-monomethyl arginine appeared to totally block inactivation of XDH/...Continue Reading

Citations

Feb 13, 2001·Clinica Chimica Acta; International Journal of Clinical Chemistry·R MartíR M Segura
Mar 1, 1996·APMIS : Acta Pathologica, Microbiologica, Et Immunologica Scandinavica·F ChenL M Demers
Oct 28, 1998·Environmental Health Perspectives·J R HoidalA B Sturrock
Oct 21, 2000·Journal of Molecular and Cellular Cardiology·J W de JongC Ceconi
Sep 30, 2015·Clinica Chimica Acta; International Journal of Clinical Chemistry·Thomas StablerVirginia B Kraus
Oct 21, 2015·Redox Biology·D Neil Granger, Peter R Kvietys
Feb 10, 2004·Biochemical and Biophysical Research Communications·Mohammad Saleem, Hiroshi Ohshima
Mar 22, 2005·Pulmonary Pharmacology & Therapeutics·Yuichi KomakiMasakazu Ichinose
Aug 17, 2004·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·R Franco-GouJ Roselló-Catafau
Aug 10, 2002·American Journal of Physiology. Lung Cellular and Molecular Physiology·Andrew J GhioJohn R Hoidal
May 4, 2018·PLoS Pathogens·Junji ChidaSuehiro Sakaguchi
Dec 9, 1997·Archives of Biochemistry and Biophysics·L S TeradaR M Wright
Oct 6, 1997·Archives of Biochemistry and Biophysics·S P KantrowC A Piantadosi
Jul 29, 1999·Chest·K A SandersJ R Hoidal

❮ Previous
Next ❯

Related Concepts

Related Feeds

American Thoracic Association Journals

Discover the latest respiratory research published by the journals from the American Thoracic Society.