DOI: 10.1073/pnas.0503590102. Dual roles for cholesterol in mammalian cells

Dual roles for cholesterol in mammalian cells

10.1073/pnas.0503590102

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

The structural features of sterols required to support mammalian cell growth have not been fully defined. Here, we use mutant CHO cells that synthesize only small amounts of cholesterol to test the capacity of various sterols to support growth. Sterols with minor modifications of the side chain (e.g., campesterol, β-sitosterol, and desmosterol) supported long-term growth of mutant cells, but sterols with more complex modifications of the side chain, the sterol nucleus, or the 3-hydroxy group did not. After 60 days in culture, the exogenous sterol comprised >90% of cellular sterols. Inactivation of residual endogenous synthesis with the squalene epoxidase inhibitor NB-598 prevented growth in β-sitosterol and greatly reduced growth in campesterol. Growth of cells cultured in β-sitosterol and NB-598 was restored by adding small amounts of cholesterol to the medium. Surprisingly, enantiomeric cholesterol also supported cell growth, even in the presence of NB-598. Thus, sterols fulfill two roles in mammalian cells: ( i ) a bulk membrane requirement in which phytosterols can substitute for cholesterol and ( ii ) other processes that specifically require small amounts of cholesterol but are not enantioselective.

Bibliography

Xu, F., Rychnovsky, S. D., Belani, J. D., Hobbs, H. H., Cohen, J. C., & Rawson, R. B. (2005). Dual roles for cholesterol in mammalian cells. Proceedings of the National Academy of Sciences, 102(41), 14551â14556.

Authors 6

Fang Xu (first)
Scott D. Rychnovsky (additional)
Jitendra D. Belani (additional)
Helen H. Hobbs (additional)
Jonathan C. Cohen (additional)
Robert B. Rawson (additional)

References 39 Referenced 113

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Dates

Type	When
Created	19 years, 11 months ago (Sept. 30, 2005, 8:33 p.m.)
Deposited	3 years, 4 months ago (April 12, 2022, 1:03 p.m.)
Indexed	1 month, 1 week ago (July 28, 2025, 5:45 p.m.)
Issued	19 years, 11 months ago (Sept. 30, 2005)
Published	19 years, 11 months ago (Sept. 30, 2005)
Published Online	19 years, 11 months ago (Sept. 30, 2005)
Published Print	19 years, 10 months ago (Oct. 11, 2005)

Funders 0

None

BibTeX

@article{Xu_2005, title={Dual roles for cholesterol in mammalian cells}, volume={102}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.0503590102}, DOI={10.1073/pnas.0503590102}, number={41}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Xu, Fang and Rychnovsky, Scott D. and Belani, Jitendra D. and Hobbs, Helen H. and Cohen, Jonathan C. and Rawson, Robert B.}, year={2005}, month=sep, pages={14551–14556} }

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