title: Nitrosothiol formation and protection against Fenton chemistry by nitric oxide-induced dinitrosyliron complex formation from anoxia-initiated cellular chelatable iron increase.
abstract: Dinitrosyliron complexes (DNIC) have been found in a variety of pathological settings associated with (•)NO. However, the iron source of cellular DNIC is unknown. Previous studies on this question using prolonged (•)NO exposure could be misleading due to the movement of intracellular iron among different sources. We here report that brief (•)NO exposure results in only barely detectable DNIC, but levels increase dramatically after 1-2 h of anoxia. This increase is similar quantitatively and temporally with increases in the chelatable iron, and brief (•)NO treatment prevents detection of this anoxia-induced increased chelatable iron by deferoxamine. DNIC formation is so rapid that it is limited by the availability of (•)NO and chelatable iron. We utilize this ability to selectively manipulate cellular chelatable iron levels and provide evidence for two cellular functions of endogenous DNIC formation, protection against anoxia-induced reactive oxygen chemistry from the Fenton reaction and formation by transnitrosation of protein nitrosothiols (RSNO). The levels of RSNO under these high chelatable iron levels are comparable with DNIC levels and suggest that under these conditions, both DNIC and RSNO are the most abundant cellular adducts of (•)NO.
authors.affiliation: From the Department of Anesthesiology and Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294, qianli@uab.edu.
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: From the Department of Anesthesiology and Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294.
authors.forename: Chuanyu
authors.initials: C
authors.lastname: Li
authors.affiliation: From the Department of Anesthesiology and Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294.
authors.forename: Harry K
authors.initials: HK
authors.lastname: Mahtani
authors.affiliation: the Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China, and.
authors.forename: Jian
authors.initials: J
authors.lastname: Du
authors.affiliation: Vestavia Hills High School, Vestavia Hills, Alabama 35216.
authors.forename: Aashka R
authors.initials: AR
authors.lastname: Patel
authors.affiliation: From the Department of Anesthesiology and Center for Free Radical Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294.
authors.forename: Jack R
authors.initials: JR
authors.lastname: Lancaster
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000502:physiology*; D002460:Cell Line; D003676:Deferoxamine / Q000494:pharmacology; D004578:Electron Spin Resonance Spectroscopy; D006861:Hydrogen Peroxide / Q000378:metabolism; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*; D009589:Nitrogen Oxides / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D026403:S-Nitrosothiols / Q000378:metabolism*
chemical_list: C045076:Fenton's reagent; D007502:Iron Chelating Agents; D009589:Nitrogen Oxides; D017382:Reactive Oxygen Species; D026403:S-Nitrosothiols; D009569:Nitric Oxide; C073661:dinitrosyl iron complex; D006861:Hydrogen Peroxide; D007501:Iron; D003676:Deferoxamine
keywords: Chelatable Iron; Dinitrosyliron Complexes; Electron Paramagnetic Resonance (EPR); Fenton Reaction; Hypoxia; Iron; Nitric Oxide; Nitrosothiol; Reactive Oxygen Species (ROS); Thiol