Orientation and vertical fluctuations of spin-labeled analogues of cholesterol and androstanol in phospholipid bilayers

Morrot, Gil; Bureau, J F; Roux, Michel; Maurin, Luc; Favre, Edith; Devaux, Philippe F.

doi:10.1016/0005-2736(87)90431-7

Cited by 18 publications

(13 citation statements)

References 19 publications

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“…5). But also a fast reorientation of the molecule is probable, and has, for instance, been found for androstane (Scheidt et al, 2003;Morrot et al, 1987). This would also agree with the finding that there is no sizable condensation effect on lipid chain order in presence of E 2 .…”

Section: Orientation and Distribution Of E 2 In Lipid Membranessupporting

confidence: 74%

Investigating the membrane orientation and transversal distribution of 17β-estradiol in lipid membranes by solid-state NMR

Scheidt

Badeau

Huster

2010

Chemistry and Physics of Lipids

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Section: Orientation and Distribution Of E 2 In Lipid Membranessupporting

confidence: 74%

Investigating the membrane orientation and transversal distribution of 17β-estradiol in lipid membranes by solid-state NMR

Scheidt

Badeau

Huster

2010

Chemistry and Physics of Lipids

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“…The localization of the doxyl group in the membrane interior was confirmed by the finding that the nitroxide label was inaccessible from the aqueous phase as it could not be reduced by ascorbate (Scheidt et al 2003). Probes with the spin-label group accessible from the aqueous phase (e.g., at C-3 as in 3b-doxyl-5a-cholestane) allow to measure cholesterol flip-flop by chemical reduction of the nitroxide radical with ascorbate (Morrot et al 1987). However, cholesterol analogues with modifications at C-3 are not regarded as faithful mimics of cholesterol.…”

Section: Spin-labeled Cholesterol Analoguesmentioning

confidence: 78%

Cholesterol Reporter Molecules

2007

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Cholesterol is a major constituent of the membranes in most eukaryotic cells where it fulfills multiple functions. Cholesterol regulates the physical state of the phospholipid bilayer, affects the activity of several membrane proteins, and is the precursor for steroid hormones and bile acids. Cholesterol plays a crucial role in the formation of membrane microdomains such as "lipid rafts" and caveolae. However, our current understanding on the membrane organization, intracellular distribution and trafficking of cholesterol is rather poor. This is mainly due to inherent difficulties to label and track this small lipid. In this review, we describe different approaches to detect cholesterol in vitro and in vivo. Cholesterol reporter molecules can be classified in two groups: cholesterol binding molecules and cholesterol analogues. The enzyme cholesterol oxidase is used for the determination of cholesterol in serum and food. Susceptibility to cholesterol oxidase can provide information about localization, transfer kinetics, or transbilayer distribution of cholesterol in membranes and cells. The polyene filipin forms a fluorescent complex with cholesterol and is commonly used to visualize the cellular distribution of free cholesterol. Perfringolysin O, a cholesterol binding cytolysin, selectively recognizes cholesterol-rich structures. Photoreactive cholesterol probes are appropriate tools to analyze or to identify cholesterol binding proteins. Among the fluorescent cholesterol analogues one can distinguish probes with intrinsic fluorescence (e.g., dehydroergosterol) from those possessing an attached fluorophore group. We summarize and critically discuss the features of the different cholesterol reporter molecules with a special focus on recent imaging approaches.

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“…From the width of the distribution a highly dynamic reorientation can be concluded, which may include even rotations of the molecule within one membrane leaflet (perpendicular to the membrane normal) as suggested in Ref. 16.…”

Section: Fig 1 Chemical Structure Of the Cholesterol Analogs Used Imentioning

confidence: 99%

“…In contrast, SL-androstane and SL-cholestane only negligibly order lipid chains, which gives these molecules more motional freedom to adopt different orientations. It has been suggested that SL-androstane may undergo rotational motions within one membrane leaflet (16).…”

Section: Sterol-induced Lipid Condensationmentioning

confidence: 99%

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The Potential of Fluorescent and Spin-labeled Steroid Analogs to Mimic Natural Cholesterol

Scheidt¹,

Müller

Herrmann

et al. 2003

Journal of Biological Chemistry

174

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Cholesterol analogs are often used to investigate lipid trafficking and membrane organization of native cholesterol. Here, the potential of various spin (doxyl moiety) and fluorescent (7-nitrobenz-2-oxa-1,3-diazol-4-yl (NBD) group) labeled cholesterol analogs as well as of fluorescent cholestatrienol and the naturally occurring dehydroergosterol to mimic the unique properties of native cholesterol in lipid membranes was studied in 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) membranes by electron paramagnetic resonance, nuclear magnetic resonance, and fluorescence spectroscopy. As cholesterol, all analogs undergo fluctuating motions of large amplitude parallel to the bilayer normal. Native cholesterol keeps a strict orientation in the membrane with the long axis parallel to the bilayer normal. Depending on the chemical modification or the position of the label, cholesterol analogs may adopt an "up-sidedown" orientation in the membrane or may even fluctuate between "upright" and up-side-down orientation by rotational motions about the short axis not typical for native cholesterol. Those analogs are not able to induce a comparable condensation of phospholipid membranes as known for native cholesterol revealed by 2 H nuclear magnetic resonance. However, cholesterol-induced lipid condensation is one of the key properties of native cholesterol, and, therefore, a well suited parameter to assess the potential of steroid analogs to mimic cholesterol. The study points to extreme caution when studying cholesterol behavior by the respective analogs. Among seven analogs investigated, only a spin-labeled cholesterol with the doxyl group at the end of the acyl chain and the fluorophore cholestatrienol mimic cholesterol satisfactorily. Dehydroergosterol has a similar upright orientation as cholesterol and could be used at low concentration (about 1 mol %), at which its lower potential to enhance lipid packing density does not perturb membrane organization.Cholesterol constitutes a major component of mammalian cellular membranes. Its correct distribution among intracellular membranes and the plasma membrane is essential for the homeostasis of mammalian cells. Thus, intracellular trafficking plays a major role in the correct disposition of internalized cholesterol and in the regulation of cholesterol efflux (for a recent review, see Ref.

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Orientation and vertical fluctuations of spin-labeled analogues of cholesterol and androstanol in phospholipid bilayers

Cited by 18 publications

References 19 publications

Investigating the membrane orientation and transversal distribution of 17β-estradiol in lipid membranes by solid-state NMR

Investigating the membrane orientation and transversal distribution of 17β-estradiol in lipid membranes by solid-state NMR

Cholesterol Reporter Molecules

The Potential of Fluorescent and Spin-labeled Steroid Analogs to Mimic Natural Cholesterol

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