Abstract:
:The transport of LDL-derived cholesterol from lysosomes to peroxisomes is facilitated by membrane contacts formed between the lysosomal protein synaptotagmin VII and the peroxisomal lipid phosphatidylinositol 4, 5-bisphosphate [PI(4,5)P2]. Here, we used RNA interference to search for regulators of PI(4,5)P2 and to study the effects of altered PI(4,5)P2 homeostasis on cholesterol transport. We found that knockdown of phosphatidylinositol 5-phosphate 4-kinase type-2 α (PIP4K2A) reduced peroxisomal PI(4,5)P2 levels, decreased lysosome-peroxisome membrane contacts, and increased accumulation of lysosomal cholesterol in human SV-589 fibroblasts. Forced expression of peroxisome-localized, kinase-active PIP4K2A in the knockdown cells reduced cholesterol accumulation, and in vitro addition of recombinant PIP4K2A restored membrane contacts. These results suggest that PIP4K2A plays a critical role in intracellular cholesterol transport by upregulating PI(4,5)P2 levels in the peroxisomal membrane. Further research into PIP4K2A activity may inform future therapeutic interventions for managing lysosomal storage disorders.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Hu A,Zhao XT,Tu H,Xiao T,Fu T,Wang Y,Liu Y,Shi XJ,Luo J,Song BLdoi
10.1194/jlr.M082149subject
Has Abstractpub_date
2018-03-01 00:00:00pages
507-514issue
3eissn
0022-2275issn
1539-7262pii
jlr.M082149journal_volume
59pub_type
杂志文章abstract::Trihydroxyoctadecenoic acids (TriHOMEs) are linoleic acid-derived oxylipins with potential physiological relevance in inflammatory processes as well as in maintaining an intact skin barrier. Due to the high number of possible TriHOME isomers with only subtle differences in their physicochemical properties, the stereoc...
journal_title:Journal of lipid research
pub_type: 杂志文章
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1996-02-01 00:00:00
abstract::Hepatocytes express on their surfaces more than one class of receptors capable of mediating the internalization of lipoproteins. However, relatively little is known about the binding characteristics of hepatic receptors for various lipoproteins, about the regulation of the receptors, and about the consequences for int...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M200187-JLR200
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1971-09-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
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更新日期:2018-09-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1995-10-01 00:00:00
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pub_type: 杂志文章
doi:10.1194/jlr.P900032-JLR200
更新日期:2009-11-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M300016-JLR200
更新日期:2003-05-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:2000-01-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1997-10-01 00:00:00
abstract::A report on the effects of primary bile acid ingestion alone or in combination with plant sterols on serum cholesterol levels, biliary lipid secretion, and bile acid metabolism. Biliary bile acid and cholesterol secretion were measured in four patients with type IIa hypercholesterolemia before and after randomized tre...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1979-01-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1982-03-01 00:00:00
abstract::Incubation of low density lipoprotein (LDL) with endothelial cells converts it to a form that is avidly degraded by macrophages via the acetyl LDL receptor. This modification has previously been shown to be accompanied by extensive breakdown of the major LDL protein (apoB-100) to smaller peptides. ApoB-100 is known to...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1987-12-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.P600002-JLR200
更新日期:2006-12-01 00:00:00
abstract::Polymorphic transformations in two saturated-unsaturated mixed acid triacylglycerols, SOS (sn -1,3-distearoyl-2-oleoylglycerol) and OSO (sn -1,3-dioleoyl-2-stearoylglycerol), have been studied by FT-IR spectroscopy using deuterated specimens in which stearoyl chains are fully deuterated. A reversible phase transition ...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1999-01-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 临床试验,杂志文章
doi:10.1194/jlr.M200439-JLR200
更新日期:2003-04-01 00:00:00
abstract::Human high density lipoprotein enriched in free cholesterol was obtained by exposing the lipoprotein to lipid dispersions having a free cholesterol/lecithin molar ratio greater than two. The metabolism of cholesterol was studied in tissue culture cells exposed to normal and cholesterol-enriched lipoproteins. Incubatio...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1978-03-01 00:00:00
abstract::Choline kinase catalyzes the phosphorylation of choline, the first step of phospholipid synthesis. Increased phosphorylation of choline is a hallmark characteristic of the malignant phenotype in a variety of neoplasms. However, in hypoxic cancer cells, choline phosphorylation is decreased. To understand the mechanism ...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M021030
更新日期:2012-01-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章,随机对照试验
doi:10.1194/jlr.M076901
更新日期:2017-11-01 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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pub_type: 杂志文章
doi:10.1194/jlr.M082891
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1998-07-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M029512
更新日期:2012-10-01 00:00:00
abstract::The potential role of the very low density lipoprotein (VLDL) receptor in mediating VLDL-induced plasminogen activator inhibitor-1 (PAI-1) expression was studied in vitro. Cultured endothelial cells incubated with VLDL showed an increased secretion of PAI-1. This response to VLDL could be completely prevented by the r...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1999-05-01 00:00:00
abstract::Cyclophosphamide injection into the fasted rabbit induces a hypertriglyceridemia (4.6 mM vs. 0.8 mM in controls) and a defect of lipoprotein lipase (LPL), as measured in post-heparin plasma (PHP). In contrast, administration of the drug into fed animals tends to increase PHP-LPL. The effects of cyclophosphamide on LPL...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::Oxidative stress promotes acute kidney injury (AKI). Higher concentrations of HDL cholesterol are associated with less AKI. To test the hypothesis that HDL antioxidant activity is associated with AKI after cardiac surgery, we quantified HDL particle size and number, paraoxonase-1 activity, and isofuran concentrations ...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1016/j.jlr.2021.100024
更新日期:2021-01-13 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:2001-07-01 00:00:00
abstract::Thus far, liver, intestine, heart, and placenta have been shown to secrete apolipoprotein (apo)B-containing lipoproteins. In the present study, we first investigated lipoproteins in human follicular fluid (FF), surrounding developing oocytes within the ovary, as well as in corresponding plasma samples (n = 12). HDL ch...
journal_title:Journal of lipid research
pub_type: 杂志文章
doi:10.1194/jlr.M005181
更新日期:2010-08-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
更新日期:1967-11-01 00:00:00