Dynamics of membrane lipid domains in neuronal cells differentiated in culture

Ottico, Elena; Prinetti, Alessandro; Prioni, Simona; Giannotta, Claudia; Basso, Luisa; Chigorno, Vanna; Sonnino, Sandro

doi:10.1194/jlr.m300247-jlr200

Cited by 75 publications

(69 citation statements)

References 49 publications

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“…Interestingly, Leppimaki et al (1998) reported that the depletion of cholesterol by HP-␤-CD stimulates sphingomyelin synthesis in cultured human skin fibroblasts. Finally, it was also proposed that the release of membrane lipids in neuronal cells by Me-␤-CD leads to a deep reorganization of the overall structure of the cell membrane, eventually leading to cell death (Ottico et al, 2003). These data are thoroughly consistent with our results on the BCECs and suggest that the toxicity of CD toward the BBB is due to the different efflux of membrane components and/or reorganization of the membrane structure.…”

Section: Downloaded Fromsupporting

confidence: 82%

Behavior of α-, β-, and γ-Cyclodextrins and Their Derivatives on an in Vitro Model of Blood-Brain Barrier

Monnaert¹,

Tilloy²,

Bricout³

et al. 2004

J Pharmacol Exp Ther

100

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Cyclodextrins (CDs) can be envisaged to cure some diseases related to the brain, but the behavior of these compounds toward the blood-brain barrier (BBB) remains largely unexplored to envisage such clinical applications. To fulfill this gap, the toxicity and endothelial permeability for native, methylated, and hydroxypropylated ␣-, ␤-, and ␥-CDs have been studied on an in vitro model of BBB. As shown by the endothelial permeability for sucrose and immunofluorescence stainings, the native CDs are the most toxic CDs (␣-Ͼ ␤-Ͼ ␥-CD). Whereas the chemical modification of ␤-CD did not affect the toxicity of this CD, differences are observed for the ␣-and ␥-CD. To determine the origin of toxicity, lipid effluxes on the brain capillary endothelial cells were performed in the presence of native CDs. It was found that ␣-CD removed phospholipids and that ␤-CD extracted phospholipids and cholesterol. ␥-CD was less lipidselective than the other CDs. Finally, the endothelial permeability of each CD has been determined. Surprisingly, no structure/ permeability relationship has been observed according to the nature and chemical modifications of CDs.Cyclodextrins (CDs) are cyclic oligosaccharides composed of 6, 7, or 8 glucose units named ␣-, ␤-, or ␥-cyclodextrin, respectively. These compounds are widely used in the pharmaceutical field to improve the dissolution rate,

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Section: Downloaded Fromsupporting

confidence: 82%

Behavior of α-, β-, and γ-Cyclodextrins and Their Derivatives on an in Vitro Model of Blood-Brain Barrier

Monnaert¹,

Tilloy²,

Bricout³

et al. 2004

J Pharmacol Exp Ther

100

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“…Such speculation is not without precedent, since studies of the oxytocin receptor have shown that binding of oxytocin is dependent on membrane interactions of the receptor with cholesterol in lipid rafts (15). Alternatively, cholesterol depletion could result in the efflux of other lipids, such as phosphatidylethanolamine, a lipid that has been shown to be a receptor of EPEC adherence (1) which is released after cholesterol depletion (33). On the other hand, EPEC forms characteristic microcolonies mediated by interbacterial binding of the bundle-forming pilus (21,26).…”

Section: Discussionmentioning

confidence: 99%

Cholesterol-Enriched Membrane Microdomains Are Required for Inducing Host Cell Cytoskeleton Rearrangements in Response to Attaching-Effacing Escherichia coli

2005

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The diarrheal pathogens enterohemorrhagic Escherichia coli (EHEC) O157:H7 strain CL56 and enteropathogenic Escherichia coli (EPEC) O127:H6 strain E2348/69 adhere intimately to epithelial cells through attaching-effacing lesions, which are characterized by rearrangements of the host cytoskeleton, intimate adherence, and destruction of microvilli. These cytoskeletal responses require activation of host signal transduction pathways. Lipid rafts are signaling microdomains enriched in sphingolipid and cholesterol in the plasma membrane. The effect of perturbing plasma membrane cholesterol on bacterial intimate adherence was assessed. Infection of both HEp-2 cells and primary skin fibroblasts with strains CL56 and E2348/69 caused characteristic rearrangements of the cytoskeleton at sites of bacterial adhesion. CL56-and E2348/69-induced cytoskeletal rearrangements were inhibited following cholesterol depletion. Addition of exogenous cholesterol to depleted HEp-2 cells restored cholesterol levels and rescued bacterially induced ␣-actinin mobilization. Quantitative bacterial adherence assays showed that EPEC adherence to HEp-2 cells was dramatically reduced following cholesterol depletion, whereas the adherence of EHEC remained high. Cytoskeletal rearrangements on skin fibroblasts obtained from children with Niemann-Pick type C disease were markedly reduced. These findings indicate that host membrane cholesterol contained in lipid rafts is necessary for the cytoskeletal rearrangements following infection with attaching-effacing Escherichia coli. Differences in initial adherence indicate divergent roles for host membrane cholesterol in the pathogenesis of EHEC and EPEC infections.

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“…The same protocol was applied for cell cultures plated on glass coverslips and fixed for 30 min in paraformaldehyde 4% except that primary antibodies were incubated for 3 h, and secondary antibodies were incubated at a dilution of 1:500. Some wells were treated with 5 mM methyl-␤-cyclodextrin for 30 min at 37°C to disrupt raft domains (Ottico et al, 2003) before fixation. The primary antibodies used were directed against: GFAP (1:1000), GLAST (1:500), MAP2 (1:200), nestin (1:500), neuronal nuclei protein (NeuN; 1:1000; Chemicon), S100␤ (1: 1000), STAT3 (1:200), and vimentin (1:1000).…”

Section: Methodsmentioning

confidence: 99%

Ciliary Neurotrophic Factor Activates Astrocytes, Redistributes Their Glutamate Transporters GLAST and GLT-1 to Raft Microdomains, and Improves Glutamate HandlingIn Vivo

Escartin¹,

Brouillet²,

Gubellini³

et al. 2006

J. Neurosci.

111

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To study the functional role of activated astrocytes in glutamate homeostasis in vivo, we used a model of sustained astrocytic activation in the rat striatum through lentiviral-mediated gene delivery of ciliary neurotrophic factor (CNTF). CNTF-activated astrocytes were hypertrophic, expressed immature intermediate filament proteins and highly glycosylated forms of their glutamate transporters GLAST and GLT-1. CNTF overexpression produced a redistribution of GLAST and GLT-1 into raft functional membrane microdomains, which are important for glutamate uptake. In contrast, CNTF had no detectable effect on the expression of a number of neuronal proteins and on the spontaneous glutamatergic transmission recorded from striatal medium spiny neurons. These results were replicated in vitro by application of recombinant CNTF on a mixed neuron/astrocyte striatal culture. Using microdialysis in the rat striatum, we found that the accumulation of extracellular glutamate induced by quinolinate (QA) was reduced threefold with CNTF. In line with this result, CNTF significantly increased QA-induced [ 18 F]-fluoro-2-deoxyglucose uptake, an indirect index of glutamate uptake by astrocytes. Together, these data demonstrate that CNTF activation of astrocytes in vivo is associated with marked phenotypic and molecular changes leading to a better handling of increased levels of extracellular glutamate. Activated astrocytes may therefore be important prosurvival agents in pathological conditions involving defects in glutamate homeostasis.

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Dynamics of membrane lipid domains in neuronal cells differentiated in culture

Cited by 75 publications

References 49 publications

Behavior of α-, β-, and γ-Cyclodextrins and Their Derivatives on an in Vitro Model of Blood-Brain Barrier

Behavior of α-, β-, and γ-Cyclodextrins and Their Derivatives on an in Vitro Model of Blood-Brain Barrier

Cholesterol-Enriched Membrane Microdomains Are Required for Inducing Host Cell Cytoskeleton Rearrangements in Response to Attaching-Effacing Escherichia coli

Ciliary Neurotrophic Factor Activates Astrocytes, Redistributes Their Glutamate Transporters GLAST and GLT-1 to Raft Microdomains, and Improves Glutamate HandlingIn Vivo

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