Oxysterols are substrates for cholesterol sulfotransferase

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 7α/7β-hydroxycholesterol and 5α,6α/5β,6β-epoxycholesterol as well as the 7α-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. 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 7α/7β-hydroxycholesterol and 5α,6α/5β,6β-epoxycholesterol as well as the 7α-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. 2-hydroxypropyl-β-cyclodextrin Cell Counting Kit-8 electrospray ionization 7-ketocholesterol 7-ketocholesterol sulfate 3′-phosphoadenosine 5′-phosphosulfate In contrast to the many studies that have established the deleterious effects of oxysterols on biologic processes (1.Brown A.J. Mander E.L. Gelissen I.C. Kritharides L. Dean R.T. Jessup W. Cholesterol and oxysterol metabolism and subcellular distribution in macrophage foam cells. Accumulation of oxidized esters in lysosomes.J. Lipid Res. 2000; 41: 226-237Abstract Full Text Full Text PDF PubMed Google Scholar, 2.Lemaire-Ewing S. Prunet C. Montange T. Vejux A. Berthier A. Bessede G. Corcos L. Gambert P. Neel D. Lizard G. Comparison of the cytotoxic, pro-oxidant and pro-inflammatory characteristics of different oxysterols.Cell Biol. Toxicol. 2005; 21: 97-114Crossref PubMed Scopus (168) Google Scholar, 3.Leonarduzzi G. Vizio B. Sottero B. Verde V. Gamba P. Mascia C. Chiarpotto E. Poli G. Biasi F. Early involvement of ROS overproduction in apoptosis induced by 7-ketocholesterol.Antioxid. Redox Signal. 2006; 8: 375-380Crossref PubMed Scopus (63) Google Scholar, 4.Smith L.L. Johnson B.H. Biological activities of oxysterols.Free Radic. Biol. Med. 1989; 7: 285-332Crossref PubMed Scopus (333) Google Scholar), there have been few studies focusing on metabolic pathways for their disposal. Of particular interest are the high levels of oxysterols in atheromas because of their association with instability and rupture, a prelude to myocardial infarction (5.Carpenter K.L. Taylor S.E. van der Veen C. Williamson B.K. Ballantine J.A. Mitchinson M.J. Lipids and oxidised lipids in human atherosclerotic lesions at different stages of development.Biochim. Biophys. Acta. 1995; 1256: 141-150Crossref PubMed Scopus (178) Google Scholar, 6.Garcia-Cruset S. Carpenter K.L. Guardiola F. Mitchinson M.J. Oxysterols in cap and core of human advanced atherosclerotic lesions.Free Radic. Res. 1999; 30: 341-350Crossref PubMed Scopus (51) Google Scholar). A major oxysterol found in atheromas as well as other tissues is 7-ketocholesterol (7-KC), which is known from cell culture studies to induce cell injury at concentrations present in vivo (7.Leonarduzzi G. Gamba P. Sottero B. Kadl A. Robbesyn F. Calogero R.A. Biasi F. Chiarpotto E. Leitinger N. Sevanian A. et al.Oxysterol-induced up-regulation of MCP-1 expression in macrophage cells.Free Radic. Biol. Med. 2005; 39: 1152-1161Crossref PubMed Scopus (72) Google Scholar, 8.Lizard G. Monier S. Cordelet C. Gesquiere L. Deckert V. Gueldry S. Largrost L. Gambert P. Characterization and comparison of the mode of cell death, apoptosis versus necrosis, induced by 7beta-hydroxycholesterol and 7-ketocholesterol in the cells of the vascular wall.Arterioscler. Thromb. Vasc. Biol. 1999; 19: 1190-1200Crossref PubMed Scopus (186) Google Scholar); for this reason, there exists a particular focus on metabolic pathways that can lead to a reduction in its toxicity. For example, it has been shown that 7-KC is a substrate for 27-hydroxylation, thus forming a more water-soluble triol that decreases the intracellular concentration of 7-KC in macrophages (9.Babiker A. Andersson O. Lund E. Xiu R.J. Deeb S. Reshef A. Leitersdorf E. Diczfalusy U. Bjorkhem I. Elimination of cholesterol in macrophages and endothelial cells by the sterol 27-hydroxylase mechanism. Comparison with high density lipoprotein-mediated reverse cholesterol transport.J. Biol. Chem. 1997; 272: 26253-26261Abstract Full Text Full Text PDF PubMed Scopus (204) Google Scholar, 10.Brown A.J. Watts G.F. Burnett J.R. Dean R.T. Jessup W. Sterol 27-hydroxylase acts on 7-ketocholesterol in human atherosclerotic lesions and macrophages in culture.J. Biol. Chem. 2000; 275: 27627-27633Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar, 11.Jessup W. Brown A.J. Novel routes for metabolism of 7-ketocholesterol.Rejuvenation Res. 2005; 8: 9-12Crossref PubMed Scopus (33) Google Scholar). We recently reported that in addition to accelerating transport, 27-hydroxylation also prevents the loss of cell viability and in coculture nullifies the toxicity of 7-KC (12.Lee J.W. Fuda H. Javitt N.B. Strott C.A. Rodriguez I.R. Expression and localization of sterol 27-hydroxylase (CYP27A1) in monkey retina.Exp. Eye Res. 2006; 83: 465-469Crossref PubMed Scopus (49) Google Scholar), findings consonant with the differential effects of oxysterols when used in combination (13.O'Sullivan A.J. O'Callaghan Y.C. O'Brien N.M. Different effects of mixtures of cholesterol oxidation products on bovine aortic endothelial cells and human monocytic U937 cells.Int. J. Toxicol. 2005; 24: 173-179Crossref PubMed Scopus (18) Google Scholar). Another potential metabolic pathway for the metabolism of oxysterols became apparent when it was found that one member of the SULT2 family of cytosolic sulfotransferases, SULT2B1b, has a particular affinity for cholesterol (14.Javitt N.B. Lee Y.C. Shimizu C. Fuda H. Strott C.A. Cholesterol and hydroxycholesterol sulfotransferases: identification, distinction from dehydroepiandrosterone sulfotransferase, and differential tissue expression.Endocrinology. 2001; 142: 2978-2984Crossref PubMed Scopus (75) Google Scholar). Although it is well recognized that sulfonation of steroid hormones affects their biologic activity (15.Hähnel R. Twaddle E. Ratajczak T. The specificity of the estrogen receptor of human uterus.J. Steroid Biochem. 1973; 4: 21-31Crossref PubMed Scopus (125) Google Scholar) and can influence their disposal (16.Bongiovanni A.M. Cohn R.M. Clinical aspects of steroid conjugation.in: Bernstein S. Solomon S. Chemical and Biological Aspects of Steroid Conjugation. Springer-Verlag, New York1970: 409-453Crossref Google Scholar), the concept that an analogous pathway exists for C27 sterols has received limited attention. Cytosolic sulfotransferases make up a superfamily of enzymes of which the SULT2 family sulfonates steroids/sterols (17.Nagata K. Yamazoe Y. Pharmacogenetics of sulfotransferase.Annu. Rev. Pharmacol. Toxicol. 2000; 40: 159-176Crossref PubMed Scopus (177) Google Scholar). The SULT2 family is further the steroid sulfotransferase to as dehydroepiandrosterone sulfotransferase, and The because of an and differential and SULT2B1b C. M.J. R.M. sulfotransferase enzymes by a PubMed Scopus Google Scholar). human and sulfonate the steroid do not cholesterol effectively as a on the other the SULT2B1b sulfonates cholesterol with the the cholesterol sulfotransferase H. Lee Y.C. Shimizu C. Javitt N.B. Strott C.A. of human sulfotransferase that of the cholesterol sulfotransferase, Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). In this present that MCF-7 cells, which highly express SULT2B1b, were significantly more resistant to the cytotoxic effect of 7-KC 293T cells, which do not express this transfection of 293T cells, were to establish that the of SULT2B1b expression correlated with a reduction in the toxicity of 7-KC. In extended the range of C27 sterols that are substrates for SULT2B1b to include the and 7α-hydroperoxide derivatives of cholesterol, thus the potential role of this pathway in modulating in vivo the injurious effects of oxysterols and also present for the that the sulfoconjugate of 7-KC in as for human atheromatous 7-KC, and were from and for were of and from of was from Chemical Cholesterol 7α-hydroperoxide was from cholesterol and to the in A. G. Comparison of cholesterol oxidation for PubMed Google Scholar). The 5′-phosphosulfate and were from and 2-hydroxypropyl-β-cyclodextrin and were from were from J. T. were from and was from and were from was from were from Cell Counting Kit-8 was from to and the were from was from and the protein was from was from was with a and is The was with a at Chemical are as the with as an was a with an electrospray ionization and to a and an The ionization for the of 7-ketocholesterol sulfate were as V. For was used as the and the was at The were on a by as a at a of the of a of of 7-KC in of was added to and at of the in at the was in of and a of on a with the sterol sulfate was with and the was on The was and the a of For for For and SULT2B1b were in as and as H. Lee Y.C. Shimizu C. Javitt N.B. Strott C.A. of human sulfotransferase that of the cholesterol sulfotransferase, Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). A and as (14.Javitt N.B. Lee Y.C. Shimizu C. Fuda H. Strott C.A. Cholesterol and hydroxycholesterol sulfotransferases: identification, distinction from dehydroepiandrosterone sulfotransferase, and differential tissue expression.Endocrinology. 2001; 142: 2978-2984Crossref PubMed Scopus (75) Google Scholar). a of and SULT2B1b in and in was were at for and at for of cholesterol sulfate as were to was the which the were and to to the of The were and of and the was by SULT2B1b was in and as A oxysterol and The of SULT2B1b used for was as cholesterol 7-KC and and were as was used to The was H. Lee Y.C. Shimizu C. Javitt N.B. Strott C.A. of human sulfotransferase that of the cholesterol sulfotransferase, Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar) as a and the and The and with were as at for by of at for at for and at for The was the to the and with and was to by of of of with and was to H. Shimizu C. Lee Y.C. H. Strott C.A. Characterization and expression of human 3′-phosphoadenosine 5′-phosphosulfate J. PubMed Google Scholar). 293T cells were by at the of MCF-7 cells were from the were at in with and in were other 293T cells were in at on the were the to the of as a was with and and for addition of the were for and to with and in 293T cells were on with and used to for sterol which was to the 7-KC 7-KCS in was added to culture and the cells were at in for this of was added to the and were for an were by the addition of of sulfate was to was at the were by 293T cells were transfected with and as a for as and in a at in and and was added to the cell culture and for at in The medium was as and for 7-KCS A was used with a at and A with a was used with a of at and to a and for an The was at were at cells were with and a cell and and with for the was and the protein concentration was the protein were to on a and to a were in a of in for with were to SULT2B1b at and with for to was added and for at with for substrate was used to the to for 293T cells were transfected as the cell cells were with and the was The was by and the of the The cholesterol was the to the and as cells. of human from an were by at the were added to of and a the were at for a of with and in that the not to The were and the was and to The was in of and and the was used for was a and a that was at A of was used at and to a with a of these it was that of 7-KCS and 7-KC of and a and of the were the and were at for from to were for and to The and were in of and were used for SULT2B1b has a for C27 in contrast to the and is in SULT2B1b is of more in 7-KC the other steroid sulfotransferases The of SULT2B1b to sulfonate C27 sterols in addition to cholesterol and 7-KC was extended to include the and of and SULT2B1b cholesterol with the its in was as Additionally, SULT2B1b was to sulfonate the 7α-hydroperoxide derivative of cholesterol, not as effectively as cholesterol, and 7-KC the of dehydroepiandrosterone sulfate by SULT2B1b was of that with the steroid sulfotransferase, not 7-KC SULT2 enzymes were as and and SULT2B1b were in 3′-phosphoadenosine 5′-phosphosulfate 2-hydroxypropyl-β-cyclodextrin and were at for and at for and were as in in a substrate of and The of human SULT2B1b, which was as a and was for substrate as cholesterol 7-KC and were at for and at for and the products were as in in a sulfonation of C27 were for at in a of and and protein concentrations were and sulfate was with (14.Javitt N.B. Lee Y.C. Shimizu C. Fuda H. Strott C.A. Cholesterol and hydroxycholesterol sulfotransferases: identification, distinction from dehydroepiandrosterone sulfotransferase, and differential tissue expression.Endocrinology. 2001; 142: 2978-2984Crossref PubMed Scopus (75) Google Scholar). in a 7-KC, SULT2 enzymes were as and and SULT2B1b were in 3′-phosphoadenosine 5′-phosphosulfate 2-hydroxypropyl-β-cyclodextrin and were at for and at for and were as in The of and The of human SULT2B1b, which was as a and was for substrate as cholesterol 7-KC and were at for and at for and the products were as in were for at in a of and and protein concentrations were and sulfate was with (14.Javitt N.B. Lee Y.C. Shimizu C. Fuda H. Strott C.A. Cholesterol and hydroxycholesterol sulfotransferases: identification, distinction from dehydroepiandrosterone sulfotransferase, and differential tissue expression.Endocrinology. 2001; 142: 2978-2984Crossref PubMed Scopus (75) Google Scholar). For the the 293T cell was because it not express 293T cells do not express which the sulfonate because is for sulfonation to 293T cells were with a for as well as a for shown in an of 7-KC to the culture medium a loss in cell viability with and the transfected cells a reduction in cell injury at concentrations of 7-KC used the at which a effect was not found a in the of cell cholesterol to the cytotoxic effect of 7-KC, cholesterol was and the no cells for cells cells for the transfected protection from loss of cell viability with transfected 293T cells was with the of SULT2B1b and the production of 7-KCS is by the of and there was no 7-KCS found in the medium of cells, in contrast to the with the transfected cells there was a in the of SULT2B1b protein transfection of 293T cells with the SULT2B1b as shown by as these were there was also a in the expression of as shown by Importantly, it was found that 7-KCS well as when added to the culture medium of 293T cells in amounts equimolar to 7-KC, not loss of cell viability for the effect of sulfonation of 7-KC was when the cytotoxicity of 7-KC was with MCF-7 cells and with 7-KC cytotoxicity with 293T cells. MCF-7 cells, which in contrast to the 293T cells highly express SULT2B1b, were significantly and more resistant to the cytotoxic effect of 7-KC 293T cells Of was the in the of MCF-7 cells, there was an apparent in cell at the concentrations of 7-KC by a in cell as the of 7-KC was further can in by the that by in the 7-KC was to the MCF-7 cells, in contrast to 293T cells, in which this was not of toxicity to the of cholesterol by by the addition of cholesterol to the 7-KC cells not as a 7-KC cholesterol not the apparent in cell at the of 7-KC not of transfected 293T cells. were and with and SULT2B1b and as in cell were and was as in of of 293T cells with 7-KC 7-KCS and cholesterol cell was by as in of of 293T MCF-7 cells with 7-KC, cell was by as in The of SULT2B1b expression by 293T and MCF-7 of the at and the at as well as the for 7-KCS and from of and of were to of Although a is there was no at the of 7-KCS in this that 7-KCS is in which was the used for that of 7-KCS have been at this can make and on the for a the of 7-KCS in one at for the other the is In this on the role that expression of SULT2B1b has in the cytotoxic effect of a effect with other We that oxysterols by such as are substrates for SULT2B1b sulfonation at the (14.Javitt N.B. Lee Y.C. Shimizu C. Fuda H. Strott C.A. Cholesterol and hydroxycholesterol sulfotransferases: identification, distinction from dehydroepiandrosterone sulfotransferase, and differential tissue expression.Endocrinology. 2001; 142: 2978-2984Crossref PubMed Scopus (75) Google Scholar). In the found that such as the and 7α-hydroperoxide of cholesterol, can also as substrates for SULT2B1b, a major role for this in the metabolism of a class of to an of cell The is of particular interest because it is a in the J.R. C. from PubMed Scopus Google Scholar, J. W. T. of retinal In of Biol. Chem. 1995; Full Text Full Text PDF PubMed Scopus Google Scholar), is when added to cell and as a of other oxysterols W. in and to 1995; PubMed Scopus Google Scholar). Oxysterols are present in tissues with a of cholesterol, a of cholesterol to oxysterol that from to U. of cholesterol oxidation products in biological PubMed Google Scholar). a concentration to the of SULT2B1b in to sulfonate 7-KC added to culture medium at which when up by the 293T and MCF-7 cells have to with the of this not to the A for this is that cholesterol is to and cytosolic cholesterol and thus to on by Thus, the of cholesterol to more apparent In it is known that there are many different and with that to enzymes a of in a cytosolic protein and its in PubMed Scopus Google Scholar). a is the of in synthesis that are by an for which cholesterol is also a the metabolism of and little is known the metabolic of other The in synthesis by the is from cholesterol by the an that is in the is further to the products and The and of Rev. Biochem. Scopus Google Scholar). the other of other sterols can in tissues other the in oxysterol metabolism that can also lead to synthesis by an pathway by the enzymes and and The and of Rev. Biochem. Scopus Google Scholar). The in synthesis by the pathway is N.B. and biologic Lipid Res. Full Text Full Text PDF PubMed Google Scholar), which is from cholesterol by the an that is in tissues (9.Babiker A. Andersson O. Lund E. Xiu R.J. Deeb S. Reshef A. Leitersdorf E. Diczfalusy U. Bjorkhem I. Elimination of cholesterol in macrophages and endothelial cells by the sterol 27-hydroxylase mechanism. Comparison with high density lipoprotein-mediated reverse cholesterol transport.J. Biol. Chem. 1997; 272: 26253-26261Abstract Full Text Full Text PDF PubMed Scopus (204) Google Scholar, Characterization of human sterol Biol. Chem. Full Text PDF PubMed Google Scholar, in the of PubMed Scopus Google Scholar). Of interest was the that cholesterol sulfate by can by at a cholesterol Bjorkhem I. K. the substrate specificity of human for and Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). The major oxysterol in human atherosclerotic is with the 7-KC A.J. Jessup W. Oxysterols and 1999; 142: Full Text Full Text PDF PubMed Scopus Google Scholar). the major oxysterol in human is with 7-KC present to a S. O. Lund E. Diczfalusy U. of cholesterol oxidation products in human by Biochem. 1995; PubMed Scopus Google Scholar, A. Diczfalusy U. of oxidized oxysterols in the human Biophys. Acta. PubMed Scopus Google Scholar). Although metabolic pathways for the metabolism of have been as in N.B. and biologic Lipid Res. Full Text Full Text PDF PubMed Google Scholar). the derivative of is a major oxysterol in from human J. of and hydroxycholesterol in the steroid of from J. Biochem. 8: PubMed Scopus Google Scholar), and is a substrate for SULT2B1b, that can in tissues that express this (14.Javitt N.B. Lee Y.C. Shimizu C. Fuda H. Strott C.A. 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PubMed Scopus Google Scholar) as well as in of macrophages by The to is 7-KCS not been in human its was highly to on this the in vivo of 7-KCS has been the potential of 7-KC as an that cell it is that little is known its metabolism in In studies 7-KC was I. K. G. and metabolism of and and Chem. A. Google Scholar, effects on and its metabolism in vivo and in Biol. Chem. Full Text PDF PubMed Google Scholar). that on the of the metabolism of 7-KC and cholesterol were in S. L. Brown A.J. metabolism of 7-ketocholesterol in for Lipid Res. 1999; 40: Full Text Full Text PDF PubMed Google Scholar) and Brown A.J. to in is and not in Biophys. Acta. 2001; PubMed Scopus Google Scholar) with the In contrast to cholesterol, which was in the 7-KC was the and as water-soluble different pathways thus cholesterol and 7-KC. of the studies of 7-KC metabolism that of the was in the to but not to in studies established that 7-KC is a substrate for (12.Lee J.W. Fuda H. Javitt N.B. Strott C.A. Rodriguez I.R. Expression and localization of sterol 27-hydroxylase (CYP27A1) in monkey retina.Exp. Eye Res. 2006; 83: 465-469Crossref PubMed Scopus (49) Google Scholar, Brown A.J. of an 7-ketocholesterol by sterol 27-hydroxylase in 2001; PubMed Scopus Google Scholar), and studies established that it is also a substrate for that is also a substrate for SULT2B1b, it is to that in the findings of the in studies the of these reported for the 7-KCS is in vivo as for human atheromatous tissues a used to a variety of is an as high levels of oxysterols found in atheromas can lead to instability and rupture, a prelude to myocardial infarction (5.Carpenter K.L. Taylor S.E. van der Veen C. Williamson B.K. Ballantine J.A. Mitchinson M.J. Lipids and oxidised lipids in human atherosclerotic lesions at different stages of development.Biochim. Biophys. Acta. 1995; 1256: 141-150Crossref PubMed Scopus (178) Google Scholar, 6.Garcia-Cruset S. Carpenter K.L. Guardiola F. Mitchinson M.J. Oxysterols in cap and core of human advanced atherosclerotic lesions.Free Radic. Res. 1999; 30: 341-350Crossref PubMed Scopus (51) Google Scholar). A major oxysterol found in atheromas as well as other tissues is 7-KC, which is known from cell culture studies to induce cell injury at concentrations present in vivo (7.Leonarduzzi G. Gamba P. Sottero B. Kadl A. Robbesyn F. Calogero R.A. Biasi F. Chiarpotto E. Leitinger N. Sevanian A. et al.Oxysterol-induced up-regulation of MCP-1 expression in macrophage cells.Free Radic. Biol. Med. 2005; 39: 1152-1161Crossref PubMed Scopus (72) Google Scholar, 8.Lizard G. Monier S. Cordelet C. Gesquiere L. Deckert V. Gueldry S. Largrost L. Gambert P. Characterization and comparison of the mode of cell death, apoptosis versus necrosis, induced by 7beta-hydroxycholesterol and 7-ketocholesterol in the cells of the vascular wall.Arterioscler. Thromb. Vasc. Biol. 1999; 19: 1190-1200Crossref PubMed Scopus (186) Google Scholar); as the sulfoconjugate of 7-KC is to cells that are to the effects of 7-KC. Thus, SULT2B1b, which is in human macrophages offers an in vivo metabolic for the of 7-KC as well as other cytotoxic it that as reported SULT2B1b can also an role in oxysterol regulation of cell by the receptor W. G. reduction of oxysterols in cells and the of Full Text Full Text PDF PubMed Scopus Google Scholar). which is by oxysterols J. et of the nuclear receptor by oxysterols a Biol. Chem. 1997; 272: Full Text Full Text PDF PubMed Scopus Google Scholar), is in the regulation of the expression of in and cholesterol metabolism and pathways metabolism and the development of Lipid Res. Full Text Full Text PDF PubMed Scopus Google Scholar). that oxysterols have a broad range of biological effects and that SULT2B1b a role the Thus, not SULT2B1b of oxysterols that are cytotoxic, it also of oxysterols in cell