Influence of the phospholipid structure on the stability of liposomes in serum

Agarwal, Kriti; Bali, Anu; Gupta, C. M.

doi:10.1016/0005-2736(86)90006-4

Cited by 29 publications

(15 citation statements)

References 23 publications

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“…Yet, surprisingly little evidence exists to support this fundamental hypothesis for cholesterol, a major structural component of cell membranes. Indeed with one exception (1), investigations with model membranes have found that sterol-lipid interactions do not affect membrane properties in an enantiospecific manner (2)(3)(4)(5)(6)(7)(8). These results suggest that although the physical properties of cholesterol are important for its membrane effects, the absolute configuration of cholesterol is not.…”

mentioning

confidence: 65%

Enantiospecificity of Cholesterol Function in Vivo

Crowder

Westover

Kumar

et al. 2001

Journal of Biological Chemistry

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The importance of the absolute configuration of cholesterol for its function in vivo is unknown. To directly test this question in vivo, we synthesized the enantiomer of cholesterol (ent-cholesterol) and tested its ability to substitute for natural cholesterol (nat-cholesterol) in the growth, viability, and behavior of Caenorhabditis elegans, a cholesterol auxotroph. First-generation animals grown on ent-cholesterol were viable with only mild behavioral defects. However, ent-cholesterol produced 100% lethality/arrest of their second generation progeny. Isotopically labeled ent-cholesterol incorporated into animals, indicating that its lethality was not secondary to cholesterol starvation. When mixed with nat-cholesterol, ent-cholesterol was not inert; rather, it antagonized the activity of nat-cholesterol. These results demonstrate for the first time that the absolute configuration of cholesterol, not just its physical properties, is essential for its functions in vivo.The two enantiomers of a molecule are nonsuperimposable mirror images of one another that have identical physical properties; they differ only in their absolute configuration around each chiral center and hence interact differently with chiral molecules. Sterols occur in nature as only one of the two possible enantiomers. Given this fact, enantiospecific interactions between sterols and other chiral molecules such as lipids and proteins are likely to occur and to be functionally important. Yet, surprisingly little evidence exists to support this fundamental hypothesis for cholesterol, a major structural component of cell membranes. Indeed with one exception (1), investigations with model membranes have found that sterol-lipid interactions do not affect membrane properties in an enantiospecific manner (2-8). These results suggest that although the physical properties of cholesterol are important for its membrane effects, the absolute configuration of cholesterol is not. In a broader context, whether the functions of cholesterol in vivo are enantiospecific has never been explicitly investigated.The nematode Caenorhabditis elegans requires exogenous sterols for viability. Several sterols satisfy this requirement; for example, cholesterol supports the growth, reproduction, and normal behavior of C. elegans (9 -13). Thus, C. elegans provides a good model to test the enantiospecificity of function of cholesterol in vivo. Toward this end, the non-naturally occurring enantiomer of cholesterol (ent-cholesterol) 1 was synthesized ( Fig. 1) and substituted for nat-cholesterol in cultures of C. elegans. We find that ent-cholesterol is incorporated into C. elegans but cannot perform the functions of nat-cholesterol. EXPERIMENTAL PROCEDURESMaterials ent-Cholesterol was synthesized as described (14). C. elegans were provided by the Caenorhabditis Genetics Center. Agarose was supplied by Sigma. Other reagents for the NGM culture plates and bacterial media including the natural cholesterol were supplied from Fisher Scientific. MethodsCulture Conditions-The C. eleg...

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mentioning

confidence: 65%

Enantiospecificity of Cholesterol Function in Vivo

Crowder

Westover

Kumar

et al. 2001

Journal of Biological Chemistry

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“…7), with identical physical properties. The rationale, therefore, is that enantiomers should behave identically in the lipid bilayer (Agarwal et al, 1986a(Agarwal et al, ,1986bArnett & Gold, 1982;Ghosh et al, 1971;Guyer & Bloch, 1983;Hermetter & Paltauf, 1982;Mannock et al, 2003;Westover & Covey, 2004). On the other hand, enantioselectivity is likely to be observed in the case of a proteinaceous binding site because proteins are composed entirely of amino acids in the L-configuration.…”

Section: E Insights From Enantiomersmentioning

confidence: 99%

Mechanisms of neurosteroid interactions with GABAA receptors

Akk¹,

Covey²,

Evers³

et al. 2007

Pharmacology & Therapeutics

147

166

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Neuroactive steroids have some of their most potent actions by augmenting the function of GABA A receptors. Endogenous steroid actions on GABA A receptors may underlie important effects on mood and behavior. Exogenous neuroactive steroids have potential as anesthetics, anticonvulsants, and neuroprotectants. We have taken multiple approaches to understand more completely the interaction of neuroactive steroids with GABA A receptors. We have developed many novel steroid analogues in this effort. Recent work has resulted in synthesis of new enantiomer analogue pairs, novel ligands that probe various properties of the steroid pharmacophore, fluorescent neuroactive steroid analogues, and photoaffinity labels. Using these tools, combined with receptor binding and electrophysiological assays, we have begun to untangle the complexity of steroid actions at this important class of ligand-gated ion channel.

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“…The latter event defined the observed release kinetics. In physiological conditions, it was shown that liposomes were stable at pH 7.4 over a time stretch much longer than the 2h used for the kinetics of the release during which only a very limited release of 5,6-CF occurs (Agarwall et al, 1986;Semple et al, 1996). In any case, these tests cannot be assimilated to test for the standard release from liposomes.…”

Section: Resultsmentioning

confidence: 99%