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Papers In Press, published online ahead of print March 8, 2007
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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.
Revised on February 26, 2007
Accepted on March 8, 2007
Oxysterols are substrates for cholesterol sulfotransferase (SULT2B1b)
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