title: Increased protein nitration in mitochondrial diseases: evidence for vessel wall involvement.
abstract: Mitochondrial diseases (MD) are heterogeneous disorders because of impairment of respiratory chain function leading to oxidative stress. We hypothesized that in MD the vascular endothelium may be affected by increased oxidative/nitrative stress causing a reduction of nitric oxide availability. We therefore, investigated the pathobiology of vasculature in MD patients by assaying the presence of 3-nitrotyrosine in muscle biopsies followed by the proteomic identification of proteins which undergo tyrosine nitration. We then measured the flow-mediated vasodilatation as a proof of altered nitric oxide generation/bioactivity. Here, we show that 3-nitrotyrosine staining is specifically located in the small vessels of muscle tissue and that the reaction is stronger and more evident in a significant percentage of vessels from MD patients as compared with controls. Eleven specific proteins which are nitrated under pathological conditions were identified; most of them are involved in energy metabolism and are located mainly in mitochondria. In MD patients the flow-mediated vasodilatation was reduced whereas baseline arterial diameters, blood flow velocity and endothelium-independent vasodilatation were similar to controls. The present results provide evidence that in MD the vessel wall is a target of increased oxidative/nitrative stress.
authors.affiliation: Department of Neurological Sciences and Vision, Section of Clinical Neurology, University of Verona, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Vattemi
authors.forename: Yehia
authors.initials: Y
authors.lastname: Mechref
authors.forename: Matteo
authors.initials: M
authors.lastname: Marini
authors.forename: Paola
authors.initials: P
authors.lastname: Tonin
authors.forename: Pietro
authors.initials: P
authors.lastname: Minuz
authors.forename: Laura
authors.initials: L
authors.lastname: Grigoli
authors.forename: Valeria
authors.initials: V
authors.lastname: Guglielmi
authors.forename: Iveta
authors.initials: I
authors.lastname: Klouckova
authors.forename: Cristiano
authors.initials: C
authors.lastname: Chiamulera
authors.forename: Alessandra
authors.initials: A
authors.lastname: Meneguzzi
authors.forename: Marzia
authors.initials: M
authors.lastname: Di Chio
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Tedesco
authors.forename: Laura
authors.initials: L
authors.lastname: Lovato
authors.forename: Maurizio
authors.initials: M
authors.lastname: Degan
authors.forename: Guido
authors.initials: G
authors.lastname: Arcaro
authors.forename: Alessandro
authors.initials: A
authors.lastname: Lechi
authors.forename: Milos V
authors.initials: MV
authors.lastname: Novotny
authors.forename: Giuliano
authors.initials: G
authors.lastname: Tomelleri
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001483:Base Sequence; D001916:Brachial Artery / Q000503:physiopathology; D016022:Case-Control Studies; D003638:Deafness / Q000235:genetics / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism; D005260:Female; D005263:Femoral Artery / Q000503:physiopathology; D006801:Humans; D007625:Kearns-Sayre Syndrome / Q000235:genetics / Q000378:metabolism; D017241:MELAS Syndrome / Q000235:genetics / Q000378:metabolism*; D017243:MERRF Syndrome / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D017354:Point Mutation; D017384:Sequence Deletion; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D014664:Vasodilation
chemical_list: C002744:3-nitrotyrosine; D014443:Tyrosine; C496314:NOS3 protein, human; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III