Evidence map›Paper›PMID 26497474›Full record

ArticleJournal of lipid research2016

ABCA1-dependent sterol release: sterol molecule specificity and potential membrane domain for HDL biogenesis.

Yoshio Yamauchi, Shinji Yokoyama, Ta-Yuan Chang

Open access · hybridAbstract read
In one paragraph

Article in Journal of lipid research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.0field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 34 citations in OpenAlex.

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  12. Blocking cholesterol storage to treat Alzheimer's disease.Exploration of neuroprotective therapy · 2021
    Article
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  18. Is ABCA1 a lipid transfer protein?Journal of lipid research · 2018
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 3 institutions in 2 countries.

Yoshio YamauchiDepartment of Biochemistry II, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755 yyoshio@med.nagoya-u.ac.jp Ta.Yuan.Chang@Dartmouth.edu.
Shinji YokoyamaNutritional Health Science Research Center and Department of Food and Nutritional Sciences, Chubu University, Kasugai 487-8501, Japan.
Ta-Yuan ChangDepartment of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755 yyoshio@med.nagoya-u.ac.jp Ta.Yuan.Chang@Dartmouth.edu.
Chubu University · JPDartmouth College · USNagoya University · JP

Funding

STRUCTURE/FUNCTION ANALYSIS OF ACATR01HL060306 · NHLBI · DARTMOUTH COLLEGE · PI CHANG, TA YUAN · 1998 to 2015
$5.5M
Impact of microglial cholesterol storage on neuroinflammationR01AG037609 · NIA · DARTMOUTH COLLEGE · PI CHANG, TA YUAN · 2010 to 2019
$3.3M
Alleviating lysosomal lipid defects in ADRD by blocking cholesterol storageR01AG063544 · NIA · DARTMOUTH COLLEGE · PI CHANG, TA YUAN · 2018 to 2021
$2.3M
NHLBI NIH HHS HL060306NHLBI NIH HHS R01 HL060306NIA NIH HHS R01 AG037609NIA NIH HHS R01 AG063544
6 · The paper itself

Abstract

Mammalian cells synthesize various sterol molecules, including the C30 sterol, lanosterol, as cholesterol precursors in the endoplasmic reticulum. The build-up of precursor sterols, including lanosterol, displays cellular toxicity. Precursor sterols are found in plasma HDL. How these structurally different sterols are released from cells is poorly understood. Here, we show that newly synthesized precursor sterols arriving at the plasma membrane (PM) are removed by extracellular apoA-I in a manner dependent on ABCA1, a key macromolecule for HDL biogenesis. Analysis of sterol molecules by GC-MS and tracing the fate of radiolabeled acetate-derived sterols in normal and mutant Niemann-Pick type C cells reveal that ABCA1 prefers newly synthesized sterols, especially lanosterol, as the substrates before they are internalized from the PM. We also show that ABCA1 resides in a cholesterol-rich membrane domain resistant to the mild detergent, Brij 98. Blocking ACAT activity increases the cholesterol contents of this domain. Newly synthesized C29/C30 sterols are transiently enriched within this domain, but rapidly disappear from this domain with a half-life of less than 1 h. Our work shows that substantial amounts of precursor sterols are transported to a certain PM domain and are removed by the ABCA1-dependent pathway.

Indexed as

AnimalsApolipoprotein A-IATP Binding Cassette Transporter 1Biological TransportCell MembraneCells, CulturedCHO CellsCholesterolCholesterol, HDLCricetulusEndoplasmic ReticulumHEK293 CellsHumansLipoproteins, HDLMembrane MicrodomainsMiceABCA1 protein, humanAPOA1 protein, humanApolipoprotein A-IATP Binding Cassette Transporter 1CholesterolCholesterol, HDLLipoproteins, HDLSterol O-Acyltransferasesterol O-acyltransferase 1Sterolsacyl-CoA:cholesterol acyltransferaseATP binding cassette transporter A1cholesterol/effluxcholesterol/traffickinghigh density lipoproteinlanosterollipid raftsNiemann-Pick disease type C

Identifiers

PMID26497474
PMCPMC4689340
OpenAlexW2178052400

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.