title: May the evaluation of nitrosative stress through selective increase of 3-nitrotyrosine proteins other than nitroalbumin and dominant tyrosine-125/136 nitrosylation of serum α-synuclein serve for diagnosis of sporadic Parkinson's disease?
abstract: Nitrosative stress, where nitrosylation of tyrosine (Tyr) leading to 3-nitrotyrosine proteins or free 3-nitrotyrosine is the most prominent change, has been proposed as a pathogenic mechanism in Parkinson's disease (PD). Levels of 3-nitrotyrosine proteins in serum and cerebrospinal fluid (CSF) of patients with PD have not been studied. Nitrosative stress-induced protein changes in serum and CSF were analyzed in patients with PD (n=54) and controls (n=40). Herein, we demonstrate the presence of nitrosative stress in serum and CSF of patients with early PD leading to selective increase of 3-nitrotyrosine proteins other than nitroalbumin, without free 3-nitrotyrosine (Hoehn-Yahr stage 1, p<0.05; stage 2, p<0.01). Among 3-nitrotyrosine proteins, nitro-α-synuclein (N-αSyn) was detected in serum, not CSF, and the sites of Tyr nitrosylation were observed to be modified in patients with early PD. Thus, the intensity of nitrosylation of Tyr125/136 residues is enhanced (stage 1, p<0.05; stage 2, p<0.01), and that of the Tyr39 site is reduced (stage 1, p<0.05), and the ratio between both parameters (α-synuclein with nitrosylated tyrosines 125 and 136 [N-αSyn-Tyr125/136]:α-synuclein with nitrosylated tyrosine 39 [N-αSyn-Tyr39] ratio) is significantly higher in patients with early PD (p<0.01). These observations lead to the hypothesis that evaluating nitrosative stress through enhanced levels of 3-nitrotyrosine proteins in serum and CSF without changes in nitroalbumin, together with the profile of tyrosine nitrosylation of serum αSyn characterized by dominant nitrosylation of Tyr125/136, could serve for the diagnosis of sporadic PD.
authors: Department of Medical Physiology, Laboratory of Molecular Neurology and Neurophysiology (BIO127), University of Seville, Seville, Spain. efespejo@us.es
authors: Emilio
authors: E
authors: Fernández
authors: José-Manuel
authors: JM
authors: García-Moreno
authors: Angel
authors: A
authors: Martín de Pablos
authors: José
authors: J
authors: Chacón
mesh_terms: D000418:Albumins / Q000737:chemistry / Q000378:metabolism; D015415:Biomarkers; D006801:Humans; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000175:diagnosis* / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism; D051844:alpha-Synuclein / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism*
chemical_list: D000418:Albumins; D015415:Biomarkers; D051844:alpha-Synuclein; C002744:3-nitrotyrosine; D014443:Tyrosine