Defect in fatty acid esterification of dolichol in Niemann-Pick type C1 mouse livers in vivo
2007 (English)In: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, ISSN 1388-1981, E-ISSN 1388-1918, Vol. 1771, no 4, 506-513 p.Article in journal (Refereed) Published
Fatty acid esterification of dolichol and cholesterol in Niemann-Pick type C 1 mouse (Balb/c NIH npcl(-/-)) livers was investigated in response to treatment with peroxisomal proliferators. These inducers have hypolipidemic properties and influence the mevalonate pathway and the intracellular transport of the final products of this biosynthetic route. Such inducers are consequently interesting to use in a disease model with defective intracellular transport of lipids. In wild-type mice, the levels of dolichol and cholesterol found as free alcohols were not changed to any great extent upon treatment with the peroxisomal inducers dehydroepiandrosterone, clofibrate and diethylhexylphtalate. In contrast, the amounts of dolichyl esters increased whereas cholesteryl esters decreased by the same treatments. The rate of enzymatic esterification of dolichol in isolated microsomes was accordingly elevated after 5- to 7-day treatments with the efficient peroxisomal proliferators DEHP and PFOA, while the corresponding esterification of cholesterol was decreased. Upon peroxisomal induction in npcl(-/-) mice, the enzymatic dolichol esterification in vitro increased whereas the low concentration of dolichyl esters remained unchanged. The results thus demonstrate that the induction of fatty acid esterification of dolichol in vivo is impaired in npcl(-/-) mouse liver. It is therefore proposed that the intracellular lipid transport defect in npcl(-/-) mouse liver disables either dolichol and/or the fatty acid from reaching the site of esterification in vivo. This proposal was strengthened by the finding that the amount of dolichol was decreased in an isolated Golgi fraction from npcl(-/-) mice.
Place, publisher, year, edition, pages
2007. Vol. 1771, no 4, 506-513 p.
dolichol, dolichyl ester, cholesteryl ester, peroxisomal proliferation, Niemann-Pick type C disease, lipid transport
Biochemistry and Molecular Biology
IdentifiersURN: urn:nbn:se:su:diva-56229DOI: 10.1016/j.bbalip.2007.01.002ISI: 000246383900007OAI: oai:DiVA.org:su-56229DiVA: diva2:410087
authorCount :22011-04-122011-04-122011-04-12Bibliographically approved