Use of cyclodextrins for manipulating cellular cholesterol content

Christian, Aimee E.; Haynes, M. Page; Phillips, Michael C.; Rothblat, George H.

doi:10.1016/s0022-2275(20)34940-3

Cited by 676 publications

(150 citation statements)

References 35 publications

Supporting

Mentioning

132

Contrasting

Unclassified

Order By: Relevance

“…An important issue for the application of Cyd to manipulate the Chol content of both model and cell membrane systems (20,49) is the question of which Cyd concentrations are allowed to be used in order to leave the membrane intact. We have investigated the extraction of fluid phase SM by Cyd as shown in Fig.…”

Section: Lipid Versus Chol Extractionmentioning

confidence: 99%

“…For example, Lange et al (16) studied the exchange of Chol between erythrocyte ghost membranes and phospholipid vesicles whereas Yeagle and Young (17) monitored Chol exchange between vesicles of different size. To overcome the problem caused by slow equilibration processes observed in these types of experiments, only recently the use of cyclodextrins (Cyds) was established (18)(19)(20)(21)(22). Niu and Litman (23) measured differential affinities of Chol for different lipids using binary Cyd-lipid vesicle systems.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Thermodynamic Comparison of the Interactions of Cholesterol with Unsaturated Phospholipid and Sphingomyelins

Tsamaloukas

Szadkowska

Heerklotz

2006

Biophysical Journal

View full text Add to dashboard Cite

A comparative analysis of the interaction of cholesterol (Chol) with palmitoyl-oleoyl-phosphatidylcholine (POPC) and sphingomyelins (SM) was performed in largely homogeneous, fluid-phase membranes at 50 degrees C. To this end, three independent assays for isothermal titration calorimetry were applied to POPC/SM/Chol mixtures. Cholesterol is solubilized by randomly methylated-beta-cyclodextrin and the uptake of Chol into (or release from) large unilamellar vesicles is measured. The affinity of Chol to a POPC/SM (1:1) membrane with 30 mol % Chol is approximately two times higher than to POPC alone; extrapolation to pure SM yields an affinity ratio of R(K) approximately 5. Bringing Chol in contact with SM is highly exothermic (-7 kJ/mol for POPC/SM (1:1), and -13 kJ/mol extrapolated to pure SM, both compared to POPC). No pronounced differences were observed between egg, bovine brain, and palmitoyl SM. With decreasing Chol content, R(K) increases and deltaH becomes more exothermic, suggesting a trend toward superlattice formation. That SM/Chol-interactions are enthalpically favorable implies that the preference of Chol for SM increases upon cooling and can induce domain formation below a certain temperature. The enthalpy gain is partially compensated by a loss in entropy in accordance with the concept of Chol-induced chain ordering, which improves intermolecular interactions (van der Waals, H-bond) but reduces conformational and motional freedom. The ability of cyclodextrin to extract sphingomyelin from membranes is twofold-weaker than for POPC.

show abstract

Section: Lipid Versus Chol Extractionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Thermodynamic Comparison of the Interactions of Cholesterol with Unsaturated Phospholipid and Sphingomyelins

Tsamaloukas

Szadkowska

Heerklotz

2006

Biophysical Journal

View full text Add to dashboard Cite

show abstract

“…␤ -Cyclodextrins have been found to be particularly efficient in solubilizing cholesterol. The high affinity of some cyclodextrins for cholesterol has made them valuable tools for the study of cholesterol flux and for the rapid and extensive manipulation of cell cholesterol content (10). Cyclodextrins, when present at high concentrations (5-100 m m ), can remove cell cholesterol at phenomenal rates (300-400%/hour) (11)(12)(13).…”

Section: Cyclodextrinsmentioning

confidence: 99%

Cell cholesterol efflux: integration of old and new observations provides new insights

Rothblat

Llera-Moya

Atger

et al. 1999

Journal of Lipid Research

443

View full text Add to dashboard Cite

Numerous studies using a variety of cell/acceptor combinations have demonstrated differences in cholesterol efflux among cells. These studies also show that different acceptors, ranging from simple molecules like cyclodextrins to serum, stimulate efflux through a variety of mechanisms. By combining early observations with data derived from recent studies, it is now possible to formulate a model for cell cholesterol efflux which proposes that an array of different mechanisms, including aqueous diffusion, lipid-free apolipoprotein membrane microsolubilization, and SR-BI-mediated cholesterol exchange contribute to cholesterol flux. In this model the relative importance of each mechanism would be determined both by the cell type and the nature of the extracellular cholesterol acceptor. -Rothblat, G.

show abstract

“…Water-soluble cholesterol forms a complex with MβCD at a saturating MβCD:cholesterol molar ratio. Thus, we used water-soluble cholesterol as cholesterol-saturated MβCD (Christian et al, 1997;Lin and Rikihisa, 2003). Synthetic lipid A was purchased from Peptide Institute (Osaka, Japan) and dissolved in dimethylsulfoxide (DMSO) at a concentration of 1 mg/mL.…”

Section: Materials and Methods Reagentsmentioning

confidence: 99%

Amphotericin B Up-regulates Lipid A-induced IL-6 ProductionviaCaspase-8

2012

View full text Add to dashboard Cite

Amphotericin B, an antifungal drug used to treat candidiasis, has been reported to induce pro-inflammatory cytokine production in cultured cells. This study investigated the effects of amphotericin B on pro-inflammatory cytokine production in response to lipid A, the bioactive component of lipopolysaccharide (LPS) in the cell walls of Gram-negative bacteria. Amphotericin B alone elicited a slight increase in interleukin (IL)-6 and IL-8 production by human gingival fibroblasts. However, amphotericin B synergistically up-regulated lipid A-induced production of IL-6 and IL-8. While amphotericin B minimally activated nuclear factor (NF)-κB, it synergistically increased lipid A-induced NF-κB activation. Pre-treatment with methyl-β-cyclodextrin (MβCD), a cholesterol-binding agent, reduced IL-6 and IL-8 production in human gingival fibroblasts. Cholesterol-saturated MβCD also reversed cytokine production, suggesting that the synergistic production of cytokines by amphotericin B and lipid A is dependent on cholesterol-rich microdomains. Amphotericin B activated caspase-8. In addition, a caspase-8 inhibitor inhibited IL-6 production by amphotericin B and lipid A. This suggests that caspase-8 is required for the synergistic production of IL-6 by amphotericin B and lipid A. Collectively, our results suggest that periodontal treatment carried out before amphotericin B treatment may protect against lipid A-induced pro-inflammatory cytokine production.

show abstract

Use of cyclodextrins for manipulating cellular cholesterol content

Cited by 676 publications

References 35 publications

Thermodynamic Comparison of the Interactions of Cholesterol with Unsaturated Phospholipid and Sphingomyelins

Thermodynamic Comparison of the Interactions of Cholesterol with Unsaturated Phospholipid and Sphingomyelins

Cell cholesterol efflux: integration of old and new observations provides new insights

Amphotericin B Up-regulates Lipid A-induced IL-6 ProductionviaCaspase-8

Contact Info

Product

Resources

About