Research article summary (published 13 Sep 2009):

Activation of membrane cholesterol by 63 amphipaths.

Full Abstract

A few membrane-intercalating amphipaths have been observed to stimulate the interaction of cholesterol with cholesterol oxidase, saponin and cyclodextrin, presumably by displacing cholesterol laterally from its phospholipid complexes. We now report that this effect, referred to as cholesterol activation, occurs with dozens of other amphipaths, including alkanols, saturated and cis- and trans-unsaturated fatty acids, fatty acid methyl esters, sphingosine derivatives, terpenes, alkyl ethers, ketones, aromatics and cyclic alkyl derivatives. The apparent potency of the agents tested ranged from 3 microM to 7 mM and generally paralleled their octanol/water partition coefficients, except that relative potency declined for compounds with >10 carbons. Some small amphipaths activated cholesterol at a membrane concentration of approximately 3 mol per 100 mol of bilayer lipids, about equimolar with the cholesterol they displaced. Lysophosphatidylserine countered the effects of all these agents, consistent with its ability to reduce the pool of active membrane cholesterol. Various amphipaths stabilized red cells against the hemolysis elicited by cholesterol depletion, presumably by substituting for the extracted sterol. The number and location of cis and trans fatty acid unsaturations and the absolute stereochemistry of enantiomer pairs had only small effects on amphipath potency. Nevertheless, potency varied approximately 7-fold within a group of diverse agents with similar partition coefficients. We infer that a wide variety of amphipaths can displace membrane cholesterol by competing stoichiometrically but with only limited specificity for weak association with phospholipids. Any number of other drugs and experimental agents might do the same.

Author information

Author/s: Lange, Yvonne (Y); Ye, Jin (J); Duban, Mark-Eugene (ME); Steck, Theodore L (TL);

Affiliation: Department of Pathology, Rush University Medical Center, Chicago, Illinois 60612, USA. ylange(-atsign-)rush.edu

Grants: GM08043 (Agency:NIGMS NIH HHS) ; HL 28448 (Agency:NHLBI NIH HHS)

Journal and publication information

Publication Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: Biochemistry (Biochemistry), published in United States. (Language: eng)

Reference: 2009-Sep; vol 48 (issue 36) : pp 8505-15

Dates: Created 2009/09/08; Completed 2009/09/28;

PMID: 19655814, status: MEDLINE (last retrieval date: 9/28/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Cells, Cultured Cholesterol - blood; chemistry Cholesterol Oxidase - blood Erythrocyte Membrane - chemistry; metabolism Hemolysis Humans

Humans Hydrophobicity Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent - blood; chemistry Intercalating Agents - chemistry; metabolism Phospholipids - blood; chemistry beta-Cyclodextrins - blood; chemistry

Associated Chemicals: Intercalating Agents (0) ; Phospholipids (0) ; beta-Cyclodextrins (0) ; methyl-beta-cyclodextrin (0) ; Cholesterol (57-88-5) ; Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent (EC 1.1.1.34) ; Cholesterol Oxidase (EC 1.1.3.6)

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