TY - JOUR
T1 - Increased protein nitration in mitochondrial diseases
T2 - Evidence for vessel wall involvement
AU - Vattemi, Gaetano
AU - Mechref, Yehia
AU - Marini, Matteo
AU - Tonin, Paola
AU - Minuz, Pietro
AU - Grigoli, Laura
AU - Guglielmi, Valeria
AU - Klouckova, Iveta
AU - Chiamulera, Cristiano
AU - Meneguzzi, Alessandra
AU - Di Chio, Marzia
AU - Tedesco, Vincenzo
AU - Lovato, Laura
AU - Degan, Maurizio
AU - Arcaro, Guido
AU - Lechi, Alessandro
AU - Novotny, Milos V.
AU - Tomelleri, Giuliano
PY - 2011/4
Y1 - 2011/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79953322206&partnerID=8YFLogxK
U2 - 10.1074/mcp.M110.002964
DO - 10.1074/mcp.M110.002964
M3 - Article
C2 - 21156839
AN - SCOPUS:79953322206
SN - 1535-9476
VL - 10
JO - Molecular and Cellular Proteomics
JF - Molecular and Cellular Proteomics
IS - 4
ER -