title: Sulphatation does not appear to be a protective mechanism to prevent oxysterol accumulation in humans and mice.
abstract: 24S- and 27-hydroxycholesterol (24OHC and 27OHC) are potent regulators of different biochemical systems in vitro and are the major circulating oxysterols. A small fraction of these oxysterols has been reported to be sulphated but there are no detailed studies. We considered the possibility that sulphatation is a protective mechanism preventing accumulation of free oxysterols. Using an accurate assay we found the sulphated fraction of 24OHC and 27OHC in circulation of adults to be less than 15% of total. In two patients with a mutation in CYP7B1 and markedly increased levels of 27OHC the sulphated fraction was 8% and 10% respectively. Infants with severe neonatal cholestasis had however markedly increased sulphate fraction of the above oxysterols. In untreated mice the degree of sulphatation of 24OHC and 27OHC in serum varied between 0 and 16%. Similar degree of sulphatation was found in two mouse models with markedly increased levels of 27OHC and 24OHC respectively. Bile duct ligated mice had higher levels of oxysterols than sham-operated controls but the sulphate fraction was not increased. We conclude that a primary increase in the levels of the oxysterols due to increased synthesis or reduced metabolism in adults and mice does not induce increased sulphatation.
authors.affiliation: Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, Stockholm, Sweden. jure.acimovic@mf.uni-lj.si
authors.forename: Jure
authors.initials: J
authors.lastname: Acimovic
authors.forename: Anita
authors.initials: A
authors.lastname: Lövgren-Sandblom
authors.forename: Maria
authors.initials: M
authors.lastname: Olin
authors.forename: Zeina
authors.initials: Z
authors.lastname: Ali
authors.forename: Maura
authors.initials: M
authors.lastname: Heverin
authors.forename: Rebecca
authors.initials: R
authors.lastname: Schüle
authors.forename: Ludger
authors.initials: L
authors.lastname: Schöls
authors.forename: Björn
authors.initials: B
authors.lastname: Fischler
authors.forename: Peter
authors.initials: P
authors.lastname: Fickert
authors.forename: Michael
authors.initials: M
authors.lastname: Trauner
authors.forename: Ingemar
authors.initials: I
authors.lastname: Björkhem
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood; D008297:Male; D051379:Mice; D008875:Middle Aged; D010084:Oxidation-Reduction
chemical_list: D006888:Hydroxycholesterols; C044563:24-hydroxycholesterol; C076996:27-hydroxycholesterol; D002784:Cholesterol