Journal
PROTEOMICS
Volume 10, Issue 10, Pages 1954-1965Publisher
WILEY
DOI: 10.1002/pmic.200900055
Keywords
Cell biology; Detergent-resistant membranes; Excitotoxicity; Lipid rafts; Neuroprotection; Statins
Funding
- Spanish Ministry of Health (Institut de Salud Carlos III) [RETICS-RD06/0026]
- Spanish Ministry of Education and Science [SAF2007-62559]
- Agencia de Gestio d'Ajuts Universitaris i de Recerca (AGAUR) [2009SGR39]
- Spanish Ministry of Education and Science
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Cell death induced by over-activation of glutamate receptors occurs in different neuropathologies. Cholesterol depletors protect from neurotoxic over-activation of glutamate receptors, and we have recently reported that this neuroprotection is associated with a reduction of the N-methyl-D-aspartate subtype of glutamate receptors in detergent-resistant membrane domains (DRM). In the present study we used comparative proteomics to further identify which proteins, besides the N-methyl-D-aspartate receptor, change its percentage of association to DRM after treatment of neurons with simvastatin. We detected 338 spots in neuronal DRM subjected to 2-DE; eleven of these spots changed its intensity after treatment with simvastatin. All 11 differential spots showed reduced intensity in simvastatin-treated samples and were identified as adipocyte plasma membrane associated protein, enolase, calretinin, coronin la, f-actin capping protein alpha 1, f-actin capping protein alpha 2, heat shock cognate protein 71, malate dehydrogenase, n-myc downregulated gene 1, prohibitin 2, Rab GDP dissociation inhibitor, translationally controlled tumor protein and voltage dependent anion selective channel protein 1. The proteins tested colocalized with the lipid raft marker caveolin-1. Interestingly, the proteins we have identified in the present study had been previously reported to play a role in cell fate and, thus, they might represent novel targets for neuroprotection.
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