title: Angiotensin-converting enzyme inhibition curbs tyrosine nitration of mitochondrial proteins in the renal cortex during the early stage of diabetes mellitus in rats.
abstract: Experiments were performed to evaluate the hypothesis that ACE (angiotensin-converting enzyme) inhibition (enalapril) suppresses 3-NT (3-nitrotyrosine) production in the renal cortex during the early stage of Type 1 DM (diabetes mellitus) in the rat. Enalapril was administered chronically for 2 weeks to subsets of STZ (streptozotocin)-induced DM and vehicle-treated sham rats. O(2)(-) (superoxide anion) and NO(x) (nitrate+nitrite) levels were measured in the media bathing renal cortical slices after 90 min incubation in vitro. SOD (superoxide dismutase) activity and 3-NT content were measured in the renal cortex homogenate. Renal cortical nitrated protein was identified by proteomic analysis. Renal cortical production of O(2)(-) and 3-NT was increased in DM rats; however, enalapril suppressed these changes. DM rats also exhibited elevated renal cortical NO(x) production and SOD activity, and these changes were magnified by enalapril treatment. 2-DE (two-dimensional gel electrophoresis)-based Western blotting revealed more than 20 spots with positive 3-NT immunoreactivity in the renal cortex of DM rats. Enalapril treatment blunted the DM-induced increase in tyrosine nitration of three proteins ACO2, GDH1 and MMSDH (aconitase 2, glutamate dehydrogenase 1 and methylmalonate-semialdehyde dehydrogenase), each of which resides in mitochondria. These data are consistent with enalapril preventing DM-induced tyrosine nitration of mitochondrial proteins by a mechanism involving suppression of oxidant production and enhancement of antioxidant capacity, including SOD activation.
authors.affiliation: Department of Medical Laboratory Sciences, Kitasato University School of Allied Health Sciences, Kanagawa 252-0373, Japan.
authors.forename: Naohito
authors.initials: N
authors.lastname: Ishii
authors.forename: Pamela K
authors.initials: PK
authors.lastname: Carmines
authors.forename: Masanori
authors.initials: M
authors.lastname: Yokoba
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Imaizumi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ichikawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Ikenagasa
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kodera
authors.forename: Masamichi
authors.initials: M
authors.lastname: Oh-Ishi
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Aoki
authors.forename: Tadakazu
authors.initials: T
authors.lastname: Maeda
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Takenaka
authors.forename: Masato
authors.initials: M
authors.lastname: Katagiri
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D006801:Humans; D007672:Kidney Cortex / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D024101:Mitochondrial Proteins / Q000378:metabolism*; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D024101:Mitochondrial Proteins; C002744:3-nitrotyrosine; D014443:Tyrosine; D007703:Peptidyl-Dipeptidase A