PMID- 24833118
OWN - NLM
STAT- MEDLINE
DCOM- 20160510
LR  - 20181202
IS  - 1879-1484 (Electronic)
IS  - 0021-9150 (Linking)
VI  - 235
IP  - 1
DP  - 2014 Jul
TI  - 3beta,5alpha,6beta-Cholestanetriol and 25-hydroxycholesterol accumulate in ATP-binding 
      cassette transporter G1 (ABCG1)-deficiency.
PG  - 122-9
LID - S0021-9150(14)00223-8 [pii]
LID - 10.1016/j.atherosclerosis.2014.04.023 [doi]
AB  - OBJECTIVE: Oxysterols are oxidized derivatives of sterols that have cytotoxic 
      effects and are potent regulators of diverse cellular functions. Efficient 
      oxysterol removal by the sub-family G member 1 of the ATP-binding cassette 
      transporters (ABCG1) is essential for cell survival and control of cellular 
      processes. However, the specific role of ABCG1 in the transport of various 
      oxysterol species has been not systematically investigated to date. Here, we 
      examined the involvement of ABCG1 in the oxysterol metabolism by studying 
      oxysterol tissue levels in a mouse model of Abcg1-deficiency. METHODS AND 
      RESULTS: Analysis of lung tissue of Abcg1(-/-) mice on a standard diet revealed 
      that 3beta,5alpha,6beta-cholestanetriol (CT) and 25-hydroxycholesterol (HC) accumulated at 
      more than 100-fold higher levels in comparison to wild-type mice. 24S-HC and 
      27-HC levels were also elevated, but were minor constituents. A radiolabeled 
      assay employing regulable ABCG1-expressing HeLa cell lines revealed that 25-HC 
      export to albumin was dependent on functional ABCG1 expression and could be 
      blocked by an excess of unlabeled 25-HC or 27-HC. In this cell line, 25-HC at low 
      doses triggered mitochondrial membrane potential, and reactive oxygen species 
      production, which are both indirect indicators of cellular energy expenditure. 
      CONCLUSION: Our results suggest that 25-HC and CT are physiologic substrates for 
      ABCG1. Excessive accumulation of these oxysterols may explain the increased rate 
      of cell death and the inflammatory phenotype observed in Abcg1-deficient animals 
      and cells.
CI  - Copyright (c) 2014 Elsevier Ireland Ltd. All rights reserved.
FAU - Engel, Thomas
AU  - Engel T
AD  - Leibniz-Institute for Arteriosclerosis Research at The Westphalian 
      Wilhelms-University, 48149 Muenster, Germany. Electronic address: 
      engeltho@uni-muenster.de.
FAU - Fobker, Manfred
AU  - Fobker M
AD  - Center for Laboratory Medicine, University Hospital Muenster, 48149 Muenster, 
      Germany.
FAU - Buchmann, Jana
AU  - Buchmann J
AD  - German Institute of Human Nutrition, Department of Experimental Diabetology, 
      14558 Potsdam-Rehbruecke, Germany.
FAU - Kannenberg, Frank
AU  - Kannenberg F
AD  - Center for Laboratory Medicine, University Hospital Muenster, 48149 Muenster, 
      Germany.
FAU - Rust, Stephan
AU  - Rust S
AD  - Leibniz-Institute for Arteriosclerosis Research at The Westphalian 
      Wilhelms-University, 48149 Muenster, Germany.
FAU - Nofer, Jerzy-Roch
AU  - Nofer JR
AD  - Center for Laboratory Medicine, University Hospital Muenster, 48149 Muenster, 
      Germany.
FAU - Schurmann, Annette
AU  - Schurmann A
AD  - German Institute of Human Nutrition, Department of Experimental Diabetology, 
      14558 Potsdam-Rehbruecke, Germany.
FAU - Seedorf, Udo
AU  - Seedorf U
AD  - Leibniz-Institute for Arteriosclerosis Research at The Westphalian 
      Wilhelms-University, 48149 Muenster, Germany.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140501
PL  - Ireland
TA  - Atherosclerosis
JT  - Atherosclerosis
JID - 0242543
RN  - 0 (ABCG1 protein, human)
RN  - 0 (ABCG1 protein, mouse)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Albumins)
RN  - 0 (Cholestanols)
RN  - 0 (Hydroxycholesterols)
RN  - 0 (Lipids)
RN  - 0 (Lipoproteins)
RN  - 0 (Reactive Oxygen Species)
RN  - 767JTD2N31 (25-hydroxycholesterol)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 1
MH  - ATP-Binding Cassette Transporters/*deficiency/genetics/metabolism
MH  - Albumins/chemistry
MH  - Animals
MH  - Biological Transport
MH  - Cell Death
MH  - Cholestanols/*chemistry
MH  - Female
MH  - HeLa Cells
MH  - Humans
MH  - Hydroxycholesterols/*chemistry
MH  - Inflammation
MH  - Lipids/chemistry
MH  - Lipoproteins/*deficiency/genetics/metabolism
MH  - Male
MH  - Membrane Potential, Mitochondrial
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mutation
MH  - Phenotype
MH  - Reactive Oxygen Species/metabolism
OTO - NOTNLM
OT  - 25-Hydroxycholesterol
OT  - 3beta,5alpha,6beta-Cholestanetriol
OT  - ATP-binding cassette transporter, G-subgroup, family member 1 (ABCG1)
OT  - Inflammation
OT  - Lipid efflux
OT  - Oxysterols
EDAT- 2014/05/17 06:00
MHDA- 2016/05/11 06:00
CRDT- 2014/05/17 06:00
PHST- 2013/07/17 00:00 [received]
PHST- 2014/04/08 00:00 [revised]
PHST- 2014/04/17 00:00 [accepted]
PHST- 2014/05/17 06:00 [entrez]
PHST- 2014/05/17 06:00 [pubmed]
PHST- 2016/05/11 06:00 [medline]
AID - S0021-9150(14)00223-8 [pii]
AID - 10.1016/j.atherosclerosis.2014.04.023 [doi]
PST - ppublish
SO  - Atherosclerosis. 2014 Jul;235(1):122-9. doi: 
      10.1016/j.atherosclerosis.2014.04.023. Epub 2014 May 1.