Document Detail


Increased protein nitration in mitochondrial diseases: evidence for vessel wall involvement.
MedLine Citation:
PMID:  21156839     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Gaetano Vattemi; Yehia Mechref; Matteo Marini; Paola Tonin; Pietro Minuz; Laura Grigoli; Valeria Guglielmi; Iveta Klouckova; Cristiano Chiamulera; Alessandra Meneguzzi; Marzia Di Chio; Vincenzo Tedesco; Laura Lovato; Maurizio Degan; Guido Arcaro; Alessandro Lechi; Milos V Novotny; Giuliano Tomelleri
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Publication Detail:
Type:  Journal Article     Date:  2010-12-14
Journal Detail:
Title:  Molecular & cellular proteomics : MCP     Volume:  10     ISSN:  1535-9484     ISO Abbreviation:  Mol. Cell Proteomics     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-04     Completed Date:  2011-07-20     Revised Date:  2012-09-24    
Medline Journal Info:
Nlm Unique ID:  101125647     Medline TA:  Mol Cell Proteomics     Country:  United States    
Other Details:
Languages:  eng     Pagination:  M110.002964     Citation Subset:  IM    
Affiliation:
Department of Neurological Sciences and Vision, Section of Clinical Neurology, University of Verona, Italy.
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Aged
Base Sequence
Brachial Artery / physiopathology
Case-Control Studies
Deafness / genetics,  metabolism
Diabetes Mellitus, Type 2 / genetics,  metabolism
Endothelium, Vascular / metabolism
Female
Femoral Artery / physiopathology
Humans
Kearns-Sayre Syndrome / genetics,  metabolism
MELAS Syndrome / genetics,  metabolism*
MERRF Syndrome / genetics,  metabolism*
Male
Middle Aged
Muscle, Skeletal / blood supply*,  metabolism
Muscle, Smooth, Vascular / metabolism
Nitric Oxide Synthase Type I / metabolism
Nitric Oxide Synthase Type III / metabolism
Point Mutation
Sequence Deletion
Tyrosine / analogs & derivatives*,  metabolism
Vasodilation
Chemical
Reg. No./Substance:
3604-79-3/3-nitrotyrosine; 55520-40-6/Tyrosine; EC 1.14.13.39/NOS3 protein, human; EC 1.14.13.39/Nitric Oxide Synthase Type I; EC 1.14.13.39/Nitric Oxide Synthase Type III
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