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.

Expression of PTRF in PC-3 Cells Modulates Cholesterol Dynamics and the Actin Cytoskeleton Impacting Secretion Pathways

“…In agreement with previous reports (22,23), our DRM fraction was highly enriched in cytoskeletal proteins and furthermore, many were reduced by PTRF expression (Table II). This in- Western blotting was performed to analyze changes in protein expression by probing with antibodies against PTRF, caveolin-1, KLK-6, and IL-6.…”

Proteomic profiling of lipid rafts in a human breast cancer model of tumorigenic progression

“…Prohibitins are primarily thought of as a mitochondrial proteins but have previously been detected in lipid raft preparations from various cell types [19,20, 21]. Furthermore, it has recently been shown that palmitoylation of prohibitin facilitates its translocation to the plasma membrane where it interacts with the lipid raft protein EHD2 [22].…”

Prohibitin-2 Binding Modulates Insulin-like Growth Factor-binding Protein-6 (IGFBP-6)-induced Rhabdomyosarcoma Cell Migration

“…PHB1 (51,53), PHB2 (56), and PHB1⅐PHB2 complexes (14,57) associate with plasma membrane lipid rafts that are believed to modulate many intracellular signaling events. Overexpression of PHB1 in 3T3-L1 fibroblasts up-regulates basal ERK MAPK signaling, leading to adipogenesis (58).…”