J. Lipid Res.
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A more recent version of this article appeared on June 1, 2007

Papers In Press, published online ahead of print March 8, 2007
J. Lipid Res., doi:10.1194/jlr.M700018-JLR200
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Submitted on January 12, 2007
Revised on February 26, 2007
Accepted on March 8, 2007

Oxysterols are substrates for cholesterol sulfotransferase (SULT2B1b)

Hirotoshi Fuda, Norman B. Javitt, Kuniko Mitamura, Shigeo Ikegawa, and Charles A. Strott

Section on Steroid Regulation, National Institue of Child Health and Human Development, Bethesda, Maryland 20892-4510

Corresponding Author: chastro{at}mail.nih.gov

Oxysterols constitute a class of cholesterol derivatives that exhibit broad biological effects ranging from cytotoxicity to regulation of nuclear receptors. The role of oxysterols such as 7-ketocholesterol (7-KC) in the development of retinal macular degeneration and atheromatous lesions is of particular interest but little is known of their metabolic fate. We establish that the steroid/sterol sulfotransferase, SULT2B1b, known to efficiently sulfonate cholesterol, also effectively sulfonates a variety of oxysterols including 7- KC. The cytotoxic effect of 7-KC on 293T cells was attenuated when these cells, which do not express SULT2B1b, were transfected with SULT2B1b cDNA. Importantly, protection from 7-KC-induced loss of cell viability with transfection correlated with synthesis of SULT2B1b protein and production of the 7-KC sulfoconjugate (7-KCS). Moreover, when 7-KCS was added to the culture medium of 293T cells in amounts equimolar to 7-KC no loss of cell viability occurred. Additionally, MCF-7 cells, which highly express SULT2B1b, were significantly more resistant to the cytotoxic effect of 7-KC. We extended the range of oxysterol substrates for SULT2B1b to include 7a/7ß-hydroxycholesterol and 5a,6a/5ß,6ß-epoxycholesterol as well as the 7a-hydroperoxide derivative of cholesterol. Thus, SULT2B1b by acting on a variety of oxysterols offers a potential pathway for modulating in vivo the injurious effects of these compounds.


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X. Li, W. M. Pandak, S. K. Erickson, Y. Ma, L. Yin, P. Hylemon, and S. Ren
Biosynthesis of the regulatory oxysterol, 5-cholesten-3{beta},25-diol 3-sulfate, in hepatocytes
J. Lipid Res., December 1, 2007; 48(12): 2587 - 2596.
[Abstract] [Full Text] [PDF]




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