|
Originally published In Press as doi:10.1074/jbc.M212503200 on March 25, 2003
J. Biol. Chem., Vol. 278, Issue 22, 19844-19851, May 30, 2003
Differential Mobilization of Newly Synthesized Cholesterol and Biosynthetic Sterol Precursors from Cells*
Sari Lusa,
Sanna Heino and
Elina Ikonen
From the
Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland
Previous work demonstrates that the biosynthetic precursor of cholesterol, desmosterol, is released from cells and that its efflux to high density lipoprotein or phosphatidylcholine vesicles is greater than that of newly synthesized cholesterol (Johnson, W. J., Fischer, R. T., Phillips, M. C., and Rothblat, G. H. (1995) J. Biol. Chem. 270, 2503725046). Here we report that the release of individual precursor sterols varies with the efflux of newly synthesized zymosterol being greater than that of lathosterol and both exceeding that of newly synthesized cholesterol when using either methyl- -cyclodextrin or complete serum as acceptors. The transfer of newly synthesized lathosterol to methyl- -cyclodextrin was inhibited by actin polymerization but not by Golgi disassembly whereas that of newly synthesized cholesterol was inhibited by both conditions. Newly synthesized lathosterol associated with cellular detergent-resistant membranes more rapidly than newly synthesized cholesterol. Upon efflux to serum, newly synthesized cholesterol precursors associated with both high and low density lipoproteins. Stimulation of the formation of direct endoplasmic reticulum-plasma membrane contacts was accompanied by enhanced efflux of newly synthesized lathosterol but not of newly synthesized cholesterol to serum acceptors. The data indicate that the efflux of cholesterol precursors differs not only from that of cholesterol but also from each other, with the more polar zymosterol being more avidly effluxed. Moreover, the results suggest that the intracellular routing of cholesterol precursors differs from that of newly synthesized cholesterol and implicates a potential role for the actin cytoskeleton and endoplasmic reticulum-plasma membrane contacts in the efflux of lathosterol.
Received for publication, December 9, 2002
, and in revised form, March 20, 2003.
* This work was supported by the Academy of Finland (Grants 48905 (to S. L.) and 43184 (to E. I.)), the Sigrid Juselius Foundation (to E. I.) and the Finnish Cultural Foundation (to S. H.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
To whom correspondence should be addressed: Dept. of Molecular Medicine, National Public Health Institute, Biomedicum Helsinki, P. O. Box 104, Haartmaninkatu 8, 00251 Helsinki, Finland. Tel.: 358-9-4744-8469; Fax: 358-9-4744-8960; E-mail: elina.ikonen{at}ktl.fi.

CiteULike Complore Connotea Del.icio.us Digg Reddit Technorati What's this?
This article has been cited by other articles:

|
 |

|
 |
 
N. Wang, L. Yvan-Charvet, D. Lutjohann, M. Mulder, T. Vanmierlo, T.-W. Kim, and A. R. Tall
ATP-binding cassette transporters G1 and G4 mediate cholesterol and desmosterol efflux to HDL and regulate sterol accumulation in the brain
FASEB J,
April 1, 2008;
22(4):
1073 - 1082.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. J. Field, K. Watt, and S. N. Mathur
Ezetimibe interferes with cholesterol trafficking from the plasma membrane to the endoplasmic reticulum in CaCo-2 cells
J. Lipid Res.,
August 1, 2007;
48(8):
1735 - 1745.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Guizzetti, J. Chen, J. F. Oram, R. Tsuji, K. Dao, T. Moller, and L. G. Costa
Ethanol Induces Cholesterol Efflux and Up-regulates ATP-binding Cassette Cholesterol Transporters in Fetal Astrocytes
J. Biol. Chem.,
June 29, 2007;
282(26):
18740 - 18749.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D Haas, J Morgenthaler, F Lacbawan, B Long, H Runz, S F Garbade, J Zschocke, R I Kelley, J G Okun, G F Hoffmann, et al.
Abnormal sterol metabolism in holoprosencephaly: studies in cultured lymphoblasts
J. Med. Genet.,
May 1, 2007;
44(5):
298 - 305.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. Ikonen
Mechanisms for cellular cholesterol transport: defects and human disease.
Physiol Rev,
October 1, 2006;
86(4):
1237 - 1261.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Megha, O. Bakht, and E. London
Cholesterol Precursors Stabilize Ordinary and Ceramide-rich Ordered Lipid Domains (Lipid Rafts) to Different Degrees: IMPLICATIONS FOR THE BLOCH HYPOTHESIS AND STEROL BIOSYNTHESIS DISORDERS
J. Biol. Chem.,
August 4, 2006;
281(31):
21903 - 21913.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. Aravindhan, C. L. Webb, M. Jaye, A. Ghosh, R. N. Willette, N. J. DiNardo, and B. M. Jucker
Assessing the effects of LXR agonists on cellular cholesterol handling: a stable isotope tracer study
J. Lipid Res.,
June 1, 2006;
47(6):
1250 - 1260.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Ridsdale, M. Denis, P.-Y. Gougeon, J. K. Ngsee, J. F. Presley, and X. Zha
Cholesterol Is Required for Efficient Endoplasmic Reticulum-to-Golgi Transport of Secretory Membrane Proteins
Mol. Biol. Cell,
April 1, 2006;
17(4):
1593 - 1605.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Vainio, M. Jansen, M. Koivusalo, T. Rog, M. Karttunen, I. Vattulainen, and E. Ikonen
Significance of Sterol Structural Specificity: DESMOSTEROL CANNOT REPLACE CHOLESTEROL IN LIPID RAFTS
J. Biol. Chem.,
January 6, 2006;
281(1):
348 - 355.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A.-L. Mutka, S. Lusa, M. D. Linder, E. Jokitalo, O. Kopra, M. Jauhiainen, and E. Ikonen
Secretion of Sterols and the NPC2 Protein from Primary Astrocytes
J. Biol. Chem.,
November 19, 2004;
279(47):
48654 - 48662.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. E. Soccio and J. L. Breslow
Intracellular Cholesterol Transport
Arterioscler. Thromb. Vasc. Biol.,
July 1, 2004;
24(7):
1150 - 1160.
[Abstract]
[Full Text]
[PDF]
|
 |
|
Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.
|
Advertisement
Advertisement
|