Alterations in energy metabolism, neuroprotection and visual signal transduction in the retina of parkinsonian, MPTP-treated monkeys

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Title: Alterations in energy metabolism, neuroprotection and visual signal transduction in the retina of parkinsonian, MPTP-treated monkeys
Authors: Campello Blasco, Laura | Esteve Rudd, Julián | Bru-Martinez, Roque | Herrero Ezquerro, María Trinidad | Fernández Villalba, Emiliano | Cuenca, Nicolás | Martín-Nieto, José
Research Group/s: Genética Humana y de Mamíferos (GHM) | Proteómica y Genómica Funcional de Plantas | Neurobiología del Sistema Visual y Terapia de Enfermedades Neurodegenerativas (NEUROVIS)
Center, Department or Service: Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología | Universidad de Alicante. Departamento de Agroquímica y Bioquímica
Keywords: Retina | Parkinson disease | Proteomics | Primates
Knowledge Area: Biología Celular | Bioquímica y Biología Molecular | Genética
Issue Date: 5-Sep-2013
Publisher: Public Library of Science (PLoS)
Citation: CAMPELLO, Laura, et al. “Alterations in energy metabolism, neuroprotection and visual signal transduction in the retina of parkinsonian, MPTP-treated monkeys.”. PLoS ONE 8(9): e74439. doi:10.1371/journal.pone.0074439
Abstract: Parkinson disease is mainly characterized by the degeneration of dopaminergic neurons in the central nervous system, including the retina. Different interrelated molecular mechanisms underlying Parkinson disease-associated neuronal death have been put forward in the brain, including oxidative stress and mitochondrial dysfunction. Systemic injection of the proneurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to monkeys elicits the appearance of a parkinsonian syndrome, including morphological and functional impairments in the retina. However, the intracellular events leading to derangement of dopaminergic and other retinal neurons in MPTP-treated animal models have not been so far investigated. Here we have used a comparative proteomics approach to identify proteins differentially expressed in the retina of MPTP-treated monkeys. Proteins were solubilized from the neural retinas of control and MPTP-treated animals, labelled separately with two different cyanine fluorophores and run pairwise on 2D DIGE gels. Out of >700 protein spots resolved and quantified, 36 were found to exhibit statistically significant differences in their expression levels, of at least ±1.4-fold, in the parkinsonian monkey retina compared with controls. Most of these spots were excised from preparative 2D gels, trypsinized and subjected to MALDI-TOF MS and LC-MS/MS analyses. Data obtained were used for protein sequence database interrogation, and 15 different proteins were successfully identified, of which 13 were underexpressed and 2 overexpressed. These proteins were involved in key cellular functional pathways such as glycolysis and mitochondrial electron transport, neuronal protection against stress and survival, and phototransduction processes. These functional categories underscore that alterations in energy metabolism, neuroprotective mechanisms and signal transduction are involved in MPTPinduced neuronal degeneration in the retina, in similarity to mechanisms thought to underlie neuronal death in the Parkinson’s diseased brain and neurodegenerative diseases of the retina proper.
Sponsor: This research was supported by grants from the Instituto de Salud Carlos III (ISCIII; PI09/1623) to JM-N, from Fundación Séneca (FS/15329/PI/10), ISCIII (PI10/02827) and Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) to MTH, and from MINECO (BFU2012-36845) and ISCIII (RETICS RD07/0062/0012 and RD12/0034/0010) to NC. JE-R and LC were recipients of predoctoral contracts from the Universidad de Alicante.
URI: http://hdl.handle.net/10045/31975
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0074439
Language: eng
Type: info:eu-repo/semantics/article
Rights: © 2013 Campello et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Peer Review: si
Publisher version: http://dx.doi.org/10.1371/journal.pone.0074439
Appears in Collections:INV - GHM - Artículos de Revistas
INV - Proteómica y Genómica Funcional de Plantas - Artículos de Revistas
INV - NEUROVIS - Artículos de Revistas

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