Ceramide structural features required to stimulate ABCA1-mediated cholesterol efflux to apolipoprotein A-I.

Ceramide structural features required to stimulate ABCA1-mediated cholesterol efflux to apolipoprotein A-I. Research Abstract Details 

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Ceramide structural features required to stimulate ABCA1-mediated cholesterol efflux to apolipoprotein A-I. Abstract Text:

Amy B Ghering,W Sean Davidson,

Ceramide is a component of the sphingomyelin cycle and a well-established lipid signaling molecule. We recently reported that ceramide specifically increased ABCA1-mediated cholesterol efflux to apolipoprotein A-I (apoA-I), a critical process that leads to the formation of cardioprotective HDL. In this report, we characterize the structural features of ceramide required for this effect. C2 dihydroceramide, which contains a fully saturated acyl chain and is commonly used as a negative control for ceramide apoptotic signaling, stimulated a 2- to 5-fold increase in ABCA1-mediated cholesterol efflux to apoA-I over a 0-60 muM concentration range without the cell toxicity apparent with native C2 ceramide. Compared with C2 ceramide, C6 and C8 ceramides with medium-length N-acyl chains showed a similar extent of efflux stimulation (a 2- to 5-fold increase) but at a higher onset concentration than the less hydrophobic C2 ceramide. In contrast, the reduced and methylated ceramide analogs, N,N-dimethyl sphingosine and N,N,N-trimethyl sphingosine, failed to stimulate cholesterol efflux. We found that changes in the native spatial orientation at either of two chiral carbon centers (or both) resulted in an approximately 50% decrease compared with native ceramide-stimulated cholesterol efflux. These data show that the overall ceramide shape and the amide bond are critical for the cholesterol efflux effect and suggest that ceramide acts through a protein-mediated pathway to affect ABCA1 activity.

Ceramide structural features required to stimulate ABCA1-mediated cholesterol efflux to apolipoprotein A-I. Publishing Authors By Initials

AB Ghering,WS Davidson,

For similar natural sciences: chemistry: chemistry, organic: isomerism: stereoisomerism research abstracts see: natural sciences: chemistry: chemistry, organic: isomerism: stereoisomerism research

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Ceramide structural features required to stimulate ABCA1-mediated cholesterol efflux to apolipoprotein A-I. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of lipid research

VOLUME: 47

Page Numbers: 2781-8

Journal Abbreviation: J. Lipid Res.

ISSN: 0022-2275

DAY: 21

MONTH: 09

YEAR: 2006

Ceramide structural features required to stimulate ABCA1-mediated cholesterol efflux to apolipoprotein A-I. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 376606

Ceramide structural features required to stimulate ABCA1-mediated cholesterol efflux to apolipoprotein A-I. Keywords Mesh Terms:

KEYWORDS: Stereoisomerism

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Ceramide structural features required to stimulate ABCA1-mediated cholesterol efflux to apolipoprotein A-I. Information

Substance Name: Cholesterol

Registry Number: 57-88-5

Grant and Affiliation Information for Ceramide structural features required to stimulate ABCA1-mediated cholesterol efflux to apolipoprotein A-I.

AFFILIATION: Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45237-0507, USA.

Country: United States

AGENCY: United States NHLBI

GRANT: HL-67093

ACRONYM: HL

MEDLINETA: J Lipid Res

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