Interaction of cholesterol with galactocerebroside and galactocerebroside-phosphatidylcholine bilayer membranes

Ruocco, Martin J.; Shipley, G. Graham

doi:10.1016/s0006-3495(84)84068-0

Cited by 77 publications

(52 citation statements)

References 38 publications

(57 reference statements)

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“…40 Theoretic and model membrane studies have demonstrated that the systematic addition of cholesterol to biologic membranes can eventually yield such sterol domains. 17,39 -45 At cholesterol levels of Ͼ50 mol % (compared with total phospholipid), an immiscible cholesterol monohydrate phase is formed with a reproducible unit-cell periodicity of 34 Å, in coexistence with the surrounding liquid crystalline lipid bilayer, 43 consistent with that observed in atherosclerotic tissues. This measurement corresponds to a tail-to-tail arrangement of the sterol, as proposed in other model membrane studies using a variety of techniques.…”

Section: Cholesterol As An Important Determinant Of Cell Membrane Strmentioning

confidence: 74%

Effects of HMG-CoA Reductase Inhibitors on Endothelial Function

2004

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Abstract-Certain pleiotropic activities reported for 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are related to reductions in cellular cholesterol biosynthesis and isoprenoid levels. In endothelial cells, these metabolic changes contribute to favorable effects on nitric oxide (NO) bioavailability. Given the essential role of NO in preserving vascular structure and function, this effect of statins is of considerable therapeutic importance. Statins have been demonstrated to restore endothelial NO production by several mechanisms, including upregulating endothelial NO synthase (eNOS) protein expression and blocking formation of reactive oxygen species. In this article, we will discuss additional ways in which statins restore endothelial NO production and improve endothelial function.(1) Statins modulate membrane microdomain formation, resulting in reduced expression of proteins that specifically inhibit eNOS activation. (2) Statins reduce sterol biosynthesis, thus interfering with the formation of pathologic microdomains, including cholesterol crystalline structures. This observation has important implications for plaque stabilization, as these microdomains contribute to cholesterol crystal formation and endothelial apoptosis. Finally, (3) statins improve endothelial function by interfering with oxidative stress pathways through both enzymatic and nonenzymatic mechanisms. The relationships between membrane microdomains, cholesterol biosynthesis, and endothelial function will be discussed.

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Section: Cholesterol As An Important Determinant Of Cell Membrane Strmentioning

confidence: 74%

Effects of HMG-CoA Reductase Inhibitors on Endothelial Function

2004

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“…7, even in the absence of sterols, CBs formed domains that persist to relatively high temperatures when mixed with 12SLPC. This is not surprising because by themselves CBs exhibit a melting temperature for the ordered (gel) to fluid state transition (up to 80°C) that is much higher than that of SM (33). This is indicative of an inherently stronger tendency of CBs to form domains in a tightly packed state.…”

Section: Effect Of Sterols On Domain Formation By Sm-sterol Effects Omentioning

confidence: 95%

Effect of the Structure of Natural Sterols and Sphingolipids on the Formation of Ordered Sphingolipid/Sterol Domains (Rafts)

Xu¹,

Bittman²,

Duportail³

et al. 2001

Journal of Biological Chemistry

494

211

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Ordered lipid domains enriched in sphingolipids and cholesterol (lipid rafts) have been implicated in numerous functions in biological membranes. We recently found that lipid domain/raft formation is dependent on the sterol component having a structure that allows tight packing with lipids having saturated acyl chains (Xu, X., and London, E. (2000) Biochemistry 39, 844 -849). In this study, the domain-promoting activities of various natural sterols were compared with that of cholesterol using both fluorescence quenching and detergent insolubility methods. Using model membranes, it was shown that, like cholesterol, both plant and fungal sterols promote the formation of tightly packed, ordered lipid domains by lipids with saturated acyl chains. Surprisingly ergosterol, a fungal sterol, and 7-dehydrocholesterol, a sterol present in elevated levels in Smith-Lemli-Opitz syndrome, were both significantly more strongly domain-promoting than cholesterol. Domain formation was also affected by the structure of the sphingolipid (or that of an equivalent "saturated" phospholipid) component. Sterols had pronounced effects on domain formation by sphingomyelin and dipalmitoylphosphatidylcholine but only a weak influence on the ability of cerebrosides to form domains. Strikingly it was found that a small amount of ceramide (3 mol %) significantly stabilized domain/raft formation. The molecular basis for, and the implications of, the effects of different sterols and sphingolipids (especially ceramide) on the behavior and biological function of rafts are discussed.There is strong evidence supporting a model of eukaryotic plasma membrane structure in which domains (rafts) rich in cholesterol and lipids with relatively saturated acyl chains (i.e. sphingolipids) co-exist with domains rich in phospholipids attached to unsaturated acyl chains (1-6). Rafts have a distinct protein composition that is especially enriched in proteins anchored to membranes by saturated acyl chains while relatively depleted of most transmembrane proteins. Rafts have been implicated in numerous cellular processes, including signal transduction, protein and lipid sorting, cellular entry by toxins and viruses, and viral budding (4, 6 -15). Thus, an understanding of the principles that underlie raft formation is important with regard to the study of eukaryotic membrane function.We have shown that sphingolipid/cholesterol domains are likely to exist in the tightly packed liquid-ordered (L o ) state, whereas unsaturated phospholipid-rich domains are more likely to be in the less ordered liquid crystalline (L ␣ ) phase even if they contain large amounts of cholesterol (16 -18). The tight packing of lipids in the L o state gives rafts their characteristic resistance to solubilization by Triton X-100 (1, 18).Cholesterol can promote separation of lipid mixtures into co-existing L ␣ and L o domains (17,19) and is critical for raft formation in cells (2-4, 6). We recently found that the ability of cholesterol to pack tightly with saturated lipids is a key to its abilit...

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“…Although S o /L d phase coexistence does play a limited role in vivo (30,31), it is nanoscopic L o /L d phase coexistence that is the hallmark of lipid rafts. Ternary lipid mixtures of sphingomyelin, phosphatidylcholine, and cholesterol result in coexisting liquid phases, but nanoscopic fluctuations are expected only close to miscibility critical points (32).…”

Section: Significancementioning

confidence: 99%

Dynamic label-free imaging of lipid nanodomains

Wit

Danial

Kukura

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

105

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Lipid rafts are submicron proteolipid domains thought to be responsible for membrane trafficking and signaling. Their small size and transient nature put an understanding of their dynamics beyond the reach of existing techniques, leading to much contention as to their exact role. Here, we exploit the differences in light scattering from lipid bilayer phases to achieve dynamic imaging of nanoscopic lipid domains without any labels. Using phase-separated droplet interface bilayers we resolve the diffusion of domains as small as 50 nm in radius and observe nanodomain formation, destruction, and dynamic coalescence with a domain lifetime of 220 ± 60 ms. Domain dynamics on this timescale suggests an important role in modulating membrane protein function.droplet interface bilayer | iSCAT | lipid nanodomains | label-free imaging | light scattering C ell membranes compartmentalize into lipid domains that enable the selective recruitment of specific proteins (1). These "lipid rafts" have been proposed to control many membrane processes including apical sorting, protein trafficking, and the clustering of proteins during signaling. The dynamic formation and destruction of lipid nanodomains are thought to provide the central mechanism to regulate this wide range of essential processes (2-4). Although many methods now provide strong evidence to support their existence in vivo (5), the combination of nanoscopic size and dynamics on millisecond timescales has placed the direct observation of their behavior beyond the scope of existing techniques. Consequently, although we know they exist, frustratingly little is known regarding their function and dynamics (6).Recent advances in fluorescence nanoscopy provide the only time-dependent information on the behavior of lipid nanodomains (7-9). Stimulated emission depletion-fluorescence correlation spectroscopy has shown cholesterol-mediated hindered nanoscale diffusion of single labeled sphingomyelin lipids that is consistent with the lipid raft hypothesis and transient binding of lipids (9). Superresolution fluorescence microscopy has also revealed protein clusters in cell membranes with 0.5-s temporal resolution (7). All of these experiments, however, are limited in temporal resolution by fluorescence, and must infer lipid nanodomains from the addition of fluorescent labels.Macroscopic phase separation in artificial lipid bilayers has been widely used to help understand the biological implications of domain formation. Different lipid phases can be visualized using fluorescence microscopy with labels that preferentially partition into a specific phase (10-12). This approach is successful for micrometer-sized domains but inevitably fails on the tens to few hundreds of nanometers scale due to limitations in phase specificity, the limited residence time of a label within a specific nanoscopic domain, and the achievable optical resolution (13). The fluorescent probe is itself an additional component that can perturb phase behavior, either directly or through photooxidation (14, 15). As ...

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Interaction of cholesterol with galactocerebroside and galactocerebroside-phosphatidylcholine bilayer membranes

Cited by 77 publications

References 38 publications

Effects of HMG-CoA Reductase Inhibitors on Endothelial Function

Effects of HMG-CoA Reductase Inhibitors on Endothelial Function

Effect of the Structure of Natural Sterols and Sphingolipids on the Formation of Ordered Sphingolipid/Sterol Domains (Rafts)

Dynamic label-free imaging of lipid nanodomains

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