Perfil proteomico de la corteza cerebral de ratas parkinsonianas por administracion de 6-ohda. Caracterizacion molecular de la subunidad ndufa10 del complejo i mitrocondrial

• Autores: Javier Muñoz Peralta
• Directores de la Tesis: Fernando J. Corrales (dir. tes.), José A. Obeso Inchausti (codir. tes.)
• Lectura: En la Universidad de Navarra ( España ) en 2007
• Idioma: español
• Tribunal Calificador de la Tesis: José María Mato (presid.), Luis Alberto Pérez Mediavilla (secret.), David Andreu Martínez (voc.), Jesús María Arizmendi Bastarrika (voc.), Javier Dotor de las Herrerías (voc.)
• Materias:
  • Química
    • Bioquímica
      • Proteínas
• Texto completo no disponible (Saber más ...)
• Resumen

  • #TITULO: PERFIL PROTEOMICO DE LA CORTEZA CEREBRAL DE RATAS PARKINSONIANAS POR ADMINISTRACIÓN DE 6-OHDA. CARACTERIZACIÓN MOLECULAR DE LA SUBUNIDAD NDUFA10 DEL COMPLEJO I MITROCONDRIAL #RESUMEN: Proteomic profiling of brain cortex in 6-OHDA treated rats. Mass spectrometric characterization of mitochondrial complex I ndufaIO variants. in the last few years the knowledge of molecular factors defining the biochemical foundations of Parkinson's disease has been importantly extended. Genetic background, protein aggregation, oxidative stress, mitochondrial disfunction, and impairment of the ubiquitine-proteasome system are alterations commonly found in PD patients as well as in different animal models. However, the precise role of each of these factors in the pathogenesis of PD is still to be uncovered. in this study we have used a combination of two dimensional electrophoresis and mass spectrometry to compare the protein conteni of brain cortex samples from control and 6-OHDA treated rats to identify differential proteins that might participate in the development of the experimental PD. Changes on proteins involved in vesicular transport have been identified, suggesting impairment of the neurotransmitter release-uptake system. Additionally, complex i subunit ndufaIO has been extensively characterized by ms/ms analysis. An intricate posttranslational modification pattern has been depicted pointing to novel regulatory mechanisms. Positions C67, H149 and H322 of ndufaIO were specially targeted by different modifications suggesting the high reactivity of these residues and their importance in the regulation of the protein. Similarly, accumulation of methylations and probably acetylations at the c-terminal region might play a role in the control of ndufaio according to mechanisms similar to those described in histones. Finally, we have identified a D/N substitution at position 120 as the biochemical difference between the two most abundant ndufaio isoforms in rats