Oxysterols are substrates for cholesterol sulfotransferase
| Autor: | Normal B. Javitt, Hirotoshi Fuda, Kuniko Mitamura, Shigeo Ikegawa, Charles A. Strott |
|---|---|
| Rok vydání: | 2007 |
| Předmět: |
Sulfotransferase
Magnetic Resonance Spectroscopy Oxysterol Cell Survival Recombinant Fusion Proteins Blotting Western QD415-436 Biology Transfection Biochemistry Cell Line chemistry.chemical_compound Endocrinology steroid/sterol sulfotransferase Humans Cytotoxic T cell Viability assay Ketocholesterols Chromatography High Pressure Liquid Dose-Response Relationship Drug Cholesterol HEK 293 cells Cell Biology Atherosclerosis Sterol Kinetics chemistry cytotoxicity Steroids lipids (amino acids peptides and proteins) Sulfotransferases 7-ketocholesterol sulfate Oxidation-Reduction |
| Zdroj: | Journal of Lipid Research, Vol 48, Iss 6, Pp 1343-1352 (2007) |
| ISSN: | 0022-2275 |
| DOI: | 10.1194/jlr.m700018-jlr200 |
| Popis: | 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 the synthesis of SULT2B1b protein and the 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 7alpha/7beta-hydroxycholesterol and 5alpha,6alpha/5beta,6beta-epoxycholesterol as well as the 7alpha-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. |
| Databáze: | OpenAIRE |
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