title: 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.
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 alpha1, f-actin capping protein alpha2, 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.
authors.affiliation: 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.
authors.forename: Jovita
authors.initials: J
authors.lastname: Ponce
authors.forename: David
authors.initials: D
authors.lastname: Brea
authors.forename: Montserrat
authors.initials: M
authors.lastname: Carrascal
authors.forename: Verónica
authors.initials: V
authors.lastname: Guirao
authors.forename: Nuria
authors.initials: N
authors.lastname: Degregorio-Rocasolano
authors.forename: Tomás
authors.initials: T
authors.lastname: Sobrino
authors.forename: José
authors.initials: J
authors.lastname: Castillo
authors.forename: Antonio
authors.initials: A
authors.lastname: Dávalos
authors.forename: Teresa
authors.initials: T
authors.lastname: Gasull
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects*; D020543:Proteome / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D019821:Simvastatin / Q000494:pharmacology*
chemical_list: D020543:Proteome; D019821:Simvastatin; D002118:Calcium