A comparison of the behavior of cholesterol and selected derivatives in mixed sterol–phospholipid Langmuir monolayers: a fluorescence microscopy study

Berring, Erin; Borrenpohl, Kimberly; Fliesler, Steven J.; Serfis, Alexa Barnoski

doi:10.1016/j.chemphyslip.2005.03.004

Cited by 53 publications

(49 citation statements)

References 58 publications

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“…Their aspect and temperature behavior are more reminiscent of gel-like domains than they are of the large, round-shaped, rapidly merging domains that are observed in the presence of cholesterol and are typical of a liquid phase. The present data are in agreement with Langmuir monolayers data showing that the molecular area in 7-DHC/dipalmitoylphosphatidylcholine fi lm is larger than for mixtures containing cholesterol ( 46 ). Another monolayer study has reported no signifi cant difference between 7-DHC and cholesterol in mixtures with EPC ( 47 ).…”

Section: Discussionsupporting

confidence: 92%

Comparison of the liquid-ordered bilayer phases containing cholesterol or 7-dehydrocholesterol in modeling Smith-Lemli-Opitz syndrome

Staneva

Chachaty

Wolf

et al. 2010

Journal of Lipid Research

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The cause was subsequently shown to be related to blockade of the ultimate reaction in the biosynthesis of cholesterol ( 2 ). Recessive mutations were described of the gene coding for 7-dehydrocholesterol reductase, the enzyme responsible for catalyzing the fi nal reduction of 7-dehydrocholesterol to cholesterol. A variety of deleterious mutations for 7-dehydrocholesterol reductase with distinct geographic distribution have been shown ( 3 ) and traced with a noticeably high frequency around 1% in healthy heterozygote carriers ( 4 ).The accumulation in fetal tissue of the metabolite 7-dehydrocholesterol (7-DHC) and derivative isomer 8-dehydrocholesterol is a specifi c biomarker for antenatal diagnosis of this severe condition ( 5 ) involving the central nervous system ( 6 ), masculinization, and facial and limb defects ( 7,8 ). Indeed the accumulation of precursors is constantly associated with a severe defi cit of the end-product cholesterol, which is also judged deleterious for embryo development. The teratology was originally studied by this laboratory in animal models treated with potent inhibitors of cholesterol biosynthesis ( 9 ). The results of in vivo studies are considered inconclusive with respect to whether the cholesterol defi cit or the accretion of aberrant sterol competing with membrane cholesterol is the underlying mechanism for teratology. The administration of a diet highly enriched in cholesterol to inhibitor-treated pregnant dams was proven to suppress malformations in the offspring ( 10 ). Nevertheless, it cannot be concluded that the defi cit in cholesterol alone is causal because negative Abstract The phase behavior of egg sphingomyelin (ESM) mixtures with cholesterol or 7-dehydrocholesterol (7-DHC) has been investigated by independent methods: fl uorescence microscopy, X-ray diffraction, and electron spin resonance spectroscopy. In giant vesicles, cholesterol-enriched domains appeared as large and clearly delineated domains assigned to a liquid-ordered (L o ) phase. The domains containing 7-DHC were smaller and had more diffuse boundaries. Separation of a gel phase assigned by X-ray examination to pure sphingomyelin domains coexisting with sterol-enriched domains was observed at temperatures less than 38°C in binary mixtures containing 10-mol% sterol. At higher sterol concentrations, the coexistence of liquid-ordered and liquid-disordered phases was evidenced in the temperature range 20°-50°C. Calculated electron density profi les indicated the location of 7-DHC was more loosely defi ned than cholesterol, which is localized precisely at a particular depth along the bilayer normal. ESR spectra of spin-labeled fatty acid partitioned in the liquid-ordered component showed a similar, high degree of order for both sterols in the center of the bilayer, but it was higher in the coexisting disordered phase for 7-DHC. The differences detected in the models of the lipid membrane matrix are said to initiate the deleterious consequences of the Smith-Lemli-Opitz syndrome. -Staneva, G., C. Chachaty, C. ...

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Section: Discussionsupporting

confidence: 92%

Comparison of the liquid-ordered bilayer phases containing cholesterol or 7-dehydrocholesterol in modeling Smith-Lemli-Opitz syndrome

Staneva

Chachaty

Wolf

et al. 2010

Journal of Lipid Research

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“…5A) indicating that lipid rafts were not present in SLO-HK. This result was surprising because the shapes of the 7-DHC and Chol molecules are very similar, and because studies using model membranes and rat brain homogenate demonstrated that both 7-DHC and Chol support formation of lipid rafts [15,16,35,36]. Consequently, we used independent methods to assess formation of DRM, which contain lipid rafts, in HK and SLO-HK.…”

Section: Discussionmentioning

confidence: 99%

“…1B) and previous studies in model membranes and brain homogenates indicated that 7-DHC supported lipid raft formation [15,16,35,36]. Consequently, we further evaluated the effect of replacing Chol with 7-DHC on the profile of proteins associated detergent resistant membranes (DRM) isolated by Triton X-100 treatment of keratinocytes.…”

Section: Lipid Raft Content Of Membranes Is Altered In Slo-hkmentioning

confidence: 94%

7-Dehydrocholesterol enhances ultraviolet A-induced oxidative stress in keratinocytes: Roles of NADPH oxidase, mitochondria, and lipid rafts

Valencia

Rajadurai

Carle

et al. 2006

Free Radical Biology and Medicine

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Long wavelength solar UVA radiation stimulates formation of reactive oxygen species (ROS) and prostaglandin E 2 (PGE 2 ), which are involved in skin photosensitivity and tumor promotion. High levels of 7-dehydrocholesterol (7-DHC), the precursor to cholesterol, cause exaggerated photosensitivity to UVA in patients with Smith-Lemli-Opitz syndrome (SLOS). Partially replacing cholesterol with 7-DHC in keratinocytes rapidly (<5 min) increased UVA-induced ROS, intracellular calcium, phospholipase A 2 activity, PGE 2 , and NADPH oxidase activity. UVA-induced ROS and PGE 2 production were inhibited in these cells by depleting the Nox1 subunit of NADPH oxidase using siRNA or using a mitochondrial radical quencher, MitoQ. Partial replacement of cholesterol with 7-DHC also disrupted membrane lipid raft domains, although depletion of cholesterol, which also disrupts lipid rafts, did not affect UVA-induced increases in ROS and PGE 2 . Phospholipid liposomes containing 7-DHC were more rapidly oxidized by a free radical mechanism than those containing cholesterol. These results indicate that 7-DHC enhances rapid UVA-induced ROS and PGE 2 formation by enhancing free radical-mediated membrane lipid oxidation and suggests that this mechanism might underlie the UVA-photosensitivity in SLOS.

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“…In sum, there do not appear to be uniformly applicable rules to predict with certainty the consequences of replacing Chol with sterols of different structures, such as 7DHC; rather, the impact of such changes tends to be a function of the particular sterol and the biological system being examined. However, recent studies from our lab using model membrane systems suggest that 7DHC has physical properties very similar to those of Chol, including packing densities and molecular volumes in mixed sterolphospholipid monolayers (Langmuir films) (33,34). These findings, in conjunction with the fact that sterols account for ,10 mol% of the total lipid in ROS membranes (29), would tend to support the conclusion that altered sterol composition is not a major factor in the observed changes in membrane fluidity or rhodopsin regenerability.…”

Section: Discussionmentioning

confidence: 99%

Alteration of retinal rod outer segment membrane fluidity in a rat model of Smith-Lemli-Opitz syndrome

Boesze‐Battaglia

Damek-Poprawa

Mitchell

et al. 2008

Journal of Lipid Research

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Smith-Lemli-Opitz syndrome (SLOS) is caused by an inherited defect in the last step in cholesterol (Chol) biosynthesis, leading to abnormal accumulation of 7-dehydrocholesterol and decreased Chol levels. Progressive retinal degeneration occurs in an animal model of SLOS, induced by treating rats with AY9944, a selective inhibitor of the enzyme affected in SLOS. Here we evaluated alterations in the biochemical and physical properties of retinal rod outer segment (ROS) membranes in this animal model. At 1 month of AY9944 treatment, there were modest alterations in fatty acid composition, but no significant differences in cis-parinaric acid (cPA) spectroscopic parameters in ROS membranes from treated versus control rats. However, at 3 months, ROS docosahexaenoic acid (DHA) content was dramatically reduced, and cPA fluorescence anisotropy values were decreased, relative to controls. Also, 1,6-diphenyl-1,3,5-hexatriene exhibited decreased rotational motion and increased orientational order in ROS membranes from 3 month-old AY9944-treated rats, relative to controls. No significant changes in protein:lipid ratios were observed; however, rhodopsin regenerability was compromised by 3 months of treatment. These findings are consistent with reduced ROS membrane fluidity in the SLOS rat model, relative to controls, primarily due to the dramatic reduction in membrane DHA levels, rather than altered sterol composition.-Boesze-Battaglia, K., M. Damek-Poprawa, D. C. Mitchell, L. Greeley, R. S. Brush, R. E. Anderson, M. J. Richards, and S. J. Fliesler. Alteration of retinal rod outer segment membrane fluidity in a rat model of Smith-LemliOpitz syndrome.

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A comparison of the behavior of cholesterol and selected derivatives in mixed sterol–phospholipid Langmuir monolayers: a fluorescence microscopy study

Cited by 53 publications

References 58 publications

Comparison of the liquid-ordered bilayer phases containing cholesterol or 7-dehydrocholesterol in modeling Smith-Lemli-Opitz syndrome

Comparison of the liquid-ordered bilayer phases containing cholesterol or 7-dehydrocholesterol in modeling Smith-Lemli-Opitz syndrome

7-Dehydrocholesterol enhances ultraviolet A-induced oxidative stress in keratinocytes: Roles of NADPH oxidase, mitochondria, and lipid rafts

Alteration of retinal rod outer segment membrane fluidity in a rat model of Smith-Lemli-Opitz syndrome

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