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?
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)...
| Autores: | , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2013 |
| País: | España |
| Institución: | Universidad de Sevilla (US) |
| Repositorio: | idUS. Depósito de Investigación de la Universidad de Sevilla |
| OAI Identifier: | oai:idus.us.es:11441/75280 |
| Acceso en línea: | https://hdl.handle.net/11441/75280 https://doi.org/10.1089/ars.2013.5250 |
| Access Level: | acceso abierto |
| Palabra clave: | Nitrosative stress Parkinson's disease |
| Sumario: | 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. |
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