Abstract：
:Vitamin E (α-tocopherol) is the major lipid-soluble antioxidant in many species. Niemann-Pick type C (NPC) disease is a lysosomal storage disorder caused by mutations in the NPC1 or NPC2 gene, which regulates lipid transport through the endocytic pathway. NPC disease is characterized by massive intracellular accumulation of unesterified cholesterol and other lipids in lysosomal vesicles. We examined the roles that NPC1/2 proteins play in the intracellular trafficking of tocopherol. Reduction of NPC1 or NPC2 expression or function in cultured cells caused a marked lysosomal accumulation of vitamin E in cultured cells. In vivo, tocopherol significantly accumulated in murine Npc1-null and Npc2-null livers, Npc2-null cerebella, and Npc1-null cerebral cortices. Plasma tocopherol levels were within the normal range in Npc1-null and Npc2-null mice, and in plasma samples from human NPC patients. The binding affinity of tocopherol to the purified sterol-binding domain of NPC1 and to purified NPC2 was significantly weaker than that of cholesterol (measurements kindly performed by R. Infante, University of Texas Southwestern Medical Center, Dallas, TX). Taken together, our observations indicate that functionality of NPC1/2 proteins is necessary for proper bioavailability of vitamin E and that the NPC pathology might involve tissue-specific perturbations of vitamin E status.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Ulatowski L,Parker R,Davidson C,Yanjanin N,Kelley TJ,Corey D,Atkinson J,Porter F,Arai H,Walkley SU,Manor Ddoi
10.1194/jlr.M015560subject
Has Abstractpub_date
2011-07-01 00:00:00pages
1400-10issue
7eissn
0022-2275issn
1539-7262pii
jlr.M015560journal_volume
52pub_type
杂志文章abstract：:There is a continuous flux of the oxysterol 27-hydroxycholesterol (27-OHC) from the circulation across the blood-brain barrier (BBB) into the brain. The major metabolite of 27-OHC in the brain is 7α-hydroxy-3-oxo-4-cholestenoic acid (7-HOCA). We confirm a recent report describing the presence of this metabolite in cer...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.P044982
更新日期：2014-02-01 00:00:00
abstract：:A rapid and accurate method is described for the assay of cholesterol ester hydrolase (CEH) activity. Aliquots of the enzyme-substrate incubation mixture are extracted into isopropanol. The free cholesterol concentration in each extract is determined enzymatically using a single aqueous reagent containing cholesterol ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
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journal_title：Journal of lipid research
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doi：
更新日期：1999-05-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1986-09-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D500005-JLR200
更新日期：2005-06-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1972-07-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1983-05-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1984-09-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1970-07-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1991-02-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R054114
更新日期：2015-06-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M044941
更新日期：2014-03-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-06-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M082891
更新日期：2018-06-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M500167-JLR200
更新日期：2005-10-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1985-07-01 00:00:00
abstract：:Native LDL (nLDL) increases expression of adhesion molecules on endothelial cells through induction of Ca(2+) mobilization. Ca(2+) mobilization is also involved in the induction of proinflammatory cytokines, important mediators involved in atherogenesis. The aim of the study was to evaluate the capacity of nLDL to aff...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.m100254-jlr200
更新日期：2002-07-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-05-01 00:00:00
abstract：:The proton NMR spectra of the N-methyl choline region of normal and lecithin:cholesterol acyltransferase (LCAT)-deficient lipoproteins and of egg yolk phosphatidylcholine-cholesterol 55:45 (mol %) vesicle mixtures have been examined in the presence and absence of manganous sulfate as a line-broadening reagent. Mangano...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-05-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M600487-JLR200
更新日期：2007-04-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1980-07-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D044636
更新日期：2014-04-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1989-08-01 00:00:00
abstract：:The inverse relationship between plasma levels of high density lipoprotein (HDL) and coronary heart disease rates has suggested that HDL might influence body stores of cholesterol. Therefore, we have investigated potential relationships between the parameters of body cholesterol metabolism and the plasma levels of HDL...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1985-09-01 00:00:00
abstract：:The isolated perfused mouse liver was utilized to evaluate the relative contribution of various molecules believed to participate in the removal of chylomicron remnants by the liver. Sixty percent of asialofetuin was removed from the perfusate per pass; bovine serum albumin was not removed. Normal mouse livers removed...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：
更新日期：1999-10-01 00:00:00
abstract：:Lecithin:cholesterol acyltransferase (LCAT) deficiency syndromes represent a group of rare genetic disorders of HDL metabolism that have been the subject of a large number of clinical, biochemical, and genetic studies. Of special interest are patients with LCAT-related disorders with severe HDL deficiency and the appa...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：
更新日期：1997-02-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.D061564
更新日期：2015-10-01 00:00:00
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journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R700005-JLR200
更新日期：2007-06-01 00:00:00
abstract：:The lipin protein family, consisting of three members, was first identified early this century. In the last few years, the lipin proteins have been shown to have important roles in glycerolipid biosynthesis and gene regulation, and mutations in the corresponding genes cause lipodystrophy, myoglobinuria, and inflammato...
journal_title：Journal of lipid research
pub_type： 杂志文章,评审
doi：10.1194/jlr.R800052-JLR200
更新日期：2009-04-01 00:00:00
abstract：:Loss of function of Niemann-Pick C1 (NPC1) leads to lysosomal free cholesterol storage, resulting in the neurodegenerative disease Niemann-Pick disease type C (NPC). Significant numbers of patients with NPC also suffer from liver disease. Currently, no treatments exist that alter patient outcome, and it is unknown if ...
journal_title：Journal of lipid research
pub_type： 杂志文章
doi：10.1194/jlr.M007211
更新日期：2010-08-01 00:00:00
