title: Iron regulates xanthine oxidase activity in the lung.
abstract: The iron chelator deferoxamine has been reported to inhibit both xanthine oxidase (XO) and xanthine dehydrogenase activity, but the relationship of this effect to the availability of iron in the cellular and tissue environment remains unexplored. XO and total xanthine oxidoreductase activity in cultured V79 cells was increased with exposure to ferric ammonium sulfate and inhibited by deferoxamine. Lung XO and total xanthine oxidoreductase activities were reduced in rats fed an iron-depleted diet and increased in rats supplemented with iron, without change in the ratio of XO to total oxidoreductase. Intratracheal injection of an iron salt or silica-iron, but not aluminum salts or silica-zinc, significantly increased rat lung XO and total xanthine oxidoreductase activities, immunoreactive xanthine oxidoreductase, and the concentration of urate in bronchoalveolar fluid. These results suggest the possibility that the production of uric acid, a major chelator of iron in extracellular fluid, is directly influenced by iron-mediated regulation of the expression and/or activity of its enzymatic source, xanthine oxidase.
authors.affiliation: National Health and Environmental Effects Research Laboratory, Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA. ghio.andy@epa.gov
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Ghio
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Kennedy
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Stonehuerner
authors.forename: Jacqueline D
authors.initials: JD
authors.lastname: Carter
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Skinner
authors.forename: Dale A
authors.initials: DA
authors.lastname: Parks
authors.forename: John R
authors.initials: JR
authors.lastname: Hoidal
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004391:Dust; D005290:Ferric Compounds / Q000008:administration & dosage / Q000494:pharmacology; D007501:Iron / Q000502:physiology*; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010088:Oxidoreductases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012822:Silicon Dioxide / Q000494:pharmacology; D014132:Trachea / Q000378:metabolism / Q000502:physiology; D014527:Uric Acid / Q000032:analysis; D014969:Xanthine Oxidase / Q000378:metabolism*
chemical_list: D004391:Dust; D005290:Ferric Compounds; D014527:Uric Acid; D012822:Silicon Dioxide; D007501:Iron; D010088:Oxidoreductases; D014969:Xanthine Oxidase; C049467:ammonium ferric sulfate