Increased protein nitration in mitochondrial diseases: Evidence for vessel wall involvement

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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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.

Original languageEnglish
JournalMolecular and Cellular Proteomics
Volume10
Issue number4
DOIs
StatePublished - Apr 2011

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