|
|
||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Journal of Lipid Research, Vol. 47, 2781-2788, December 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology
Department of Pathology and Laboratory Medicine, University of Cincinnati, Cincinnati, OH 45237-0507
Published, JLR Papers in Press, September 21, 2006.
1 To whom correspondence should be addressed. e-mail: sean.davidson{at}uc.edu
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 060 µM 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
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.
Supplementary key words chemical structure stereochemistry ATP binding cassette type A1
Abbreviations: apoA-I, apolipoprotein A-I; CAPK, ceramide-activated protein kinase; CAPP, ceramide-activated protein phosphatase; DMS, N,N-dimethyl sphingosine; PVDF, polyvinylidene difluoride; TMS, N,N,N-trimethyl sphingosine
![]()
CiteULike
Complore
Connotea
Del.icio.us
Digg
Reddit
Technorati What's this?
This article has been cited by other articles:
![]() |
D. A. Evseenko, P. Murthi, J. W. Paxton, G. Reid, B. S. Emerald, K. M. Mohankumar, P. E. Lobie, S. P. Brennecke, B. Kalionis, and J. A. Keelan The ABC transporter BCRP/ABCG2 is a placental survival factor, and its expression is reduced in idiopathic human fetal growth restriction FASEB J, November 1, 2007; 21(13): 3592 - 3605. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |