Author/Editor | Ačimovič, Jure; Lövgren-Sandblom, Anita; Olin, Maria; Ali, Zeina | |
Title | Sulphatation does not appear to be a protective mechanism to prevent oxysterol accumulation in humans and mice | |
Type | članek | |
Vol. and No. | Letnik 8, št. 7 | |
Publication year | 2013 | |
ISSN | 1932-6203 - PloS one | |
Language | eng | |
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. | |
Keywords | biochemical systems regulators metabolism biokemijski sistemi regulatorji metabolizem |