The effect of simvastatin on the proteome of detergent‐resistant membrane domains: Decreases of specific proteins previously related to cytoskeleton regulation,calcium homeostasis and cell fate |
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Authors: | Jovita Ponce David Brea Montserrat Carrascal Verónica Guirao Nuria DeGregorio‐Rocasolano Tomás Sobrino José Castillo Antonio Dávalos Teresa Gasull |
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Affiliation: | 1. Cellular and Molecular Neurobiology Research Group and Grup de Recerca en Neurociencies del IGTP, Department of Neurosciences, Fundació Institut d'Investigació en Ciències de la Salut Germans Trias I Pujol‐Universitat Autónoma de Barcelona, Badalona, Spain;2. Department of Neurology, Clinical Neuroscience Research Laboratory, Hospital Clínico Universitario, University of Santiago de Compostela, Santiago de Compostela, Spain;3. CSIC/UAB Proteomics Laboratory, Department of Experimental Pathology, IIBB‐CSIC, IDIBAPS, Edifici M‐UAB, Barcelona, Spain |
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Abstract: | 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 1a, f‐actin capping protein α1, f‐actin capping protein α2, 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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Keywords: | Cell biology Detergent‐resistant membranes Excitotoxicity Lipid rafts Neuroprotection Statins |
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