PMID- 28315462
OWN - NLM
STAT- MEDLINE
DCOM- 20170814
LR  - 20220803
IS  - 1388-1981 (Print)
IS  - 1388-1981 (Linking)
VI  - 1862
IP  - 6
DP  - 2017 Jun
TI  - Implications of cerebrovascular ATP-binding cassette transporter G1 (ABCG1) and 
      apolipoprotein M in cholesterol transport at the blood-brain barrier.
PG  - 573-588
LID - S1388-1981(17)30051-3 [pii]
LID - 10.1016/j.bbalip.2017.03.003 [doi]
AB  - Impaired cholesterol/lipoprotein metabolism is linked to neurodegenerative 
      diseases such as Alzheimer's disease (AD). Cerebral cholesterol homeostasis is 
      maintained by the highly efficient blood-brain barrier (BBB) and flux of the 
      oxysterols 24(S)-hydroxycholesterol and 27-hydroxycholesterol, potent 
      liver-X-receptor (LXR) activators. HDL and their apolipoproteins are crucial for 
      cerebral lipid transfer, and loss of ATP binding cassette transporters (ABC)G1 
      and G4 results in toxic accumulation of oxysterols in the brain. The 
      HDL-associated apolipoprotein (apo)M is positively correlated with pre-beta HDL 
      formation in plasma; its presence and function in the brain was thus far unknown. 
      Using an in vitro model of the BBB, we examined expression, regulation, and 
      functions of ABCG1, ABCG4, and apoM in primary porcine brain capillary 
      endothelial cells (pBCEC). RT Q-PCR analyses and immunoblotting revealed that in 
      addition to ABCA1 and scavenger receptor, class B, type I (SR-BI), pBCEC express 
      high levels of ABCG1, which was up-regulated by LXR activation. Immunofluorescent 
      staining, site-specific biotinylation and immunoprecipitation revealed that ABCG1 
      is localized both to early and late endosomes and on apical and basolateral 
      plasma membranes. Using siRNA interference to silence ABCG1 (by 50%) reduced 
      HDL-mediated [(3)H]-cholesterol efflux (by 50%) but did not reduce 
      [(3)H]-24(S)-hydroxycholesterol efflux. In addition to apoA-I, pBCEC express and 
      secrete apoM mainly to the basolateral (brain) compartment. HDL enhanced 
      expression and secretion of apoM by pBCEC, apoM-enriched HDL promoted cellular 
      cholesterol efflux more efficiently than apoM-free HDL, while apoM-silencing 
      diminished cellular cholesterol release. We suggest that ABCG1 and apoM are 
      centrally involved in regulation of cholesterol metabolism/turnover at the BBB.
CI  - Copyright (c) 2017 Elsevier B.V. All rights reserved.
FAU - Kober, Alexandra Carmen
AU  - Kober AC
AD  - Institute of Pathophysiology and Immunology, Medical University of Graz, Graz, 
      Austria.
FAU - Manavalan, Anil Paul Chirackal
AU  - Manavalan APC
AD  - Institute of Pathophysiology and Immunology, Medical University of Graz, Graz, 
      Austria.
FAU - Tam-Amersdorfer, Carmen
AU  - Tam-Amersdorfer C
AD  - Institute of Pathophysiology and Immunology, Medical University of Graz, Graz, 
      Austria.
FAU - Holmer, Andreas
AU  - Holmer A
AD  - Department of Translational Medicine, University Hospital SUS, Malmo, Lund 
      University, Sweden.
FAU - Saeed, Ahmed
AU  - Saeed A
AD  - Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska 
      University Hospital, Karolinska Institute Huddinge, Huddinge, Sweden.
FAU - Fanaee-Danesh, Elham
AU  - Fanaee-Danesh E
AD  - Institute of Pathophysiology and Immunology, Medical University of Graz, Graz, 
      Austria.
FAU - Zandl, Martina
AU  - Zandl M
AD  - Institute of Pathophysiology and Immunology, Medical University of Graz, Graz, 
      Austria.
FAU - Albrecher, Nicole Maria
AU  - Albrecher NM
AD  - Institute of Pathophysiology and Immunology, Medical University of Graz, Graz, 
      Austria.
FAU - Bjorkhem, Ingemar
AU  - Bjorkhem I
AD  - Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska 
      University Hospital, Karolinska Institute Huddinge, Huddinge, Sweden.
FAU - Kostner, Gerhard M
AU  - Kostner GM
AD  - Institute of Molecular Biology and Biochemistry, Medical University of Graz, 
      Graz, Austria.
FAU - Dahlback, Bjorn
AU  - Dahlback B
AD  - Department of Translational Medicine, University Hospital SUS, Malmo, Lund 
      University, Sweden.
FAU - Panzenboeck, Ute
AU  - Panzenboeck U
AD  - Institute of Pathophysiology and Immunology, Medical University of Graz, Graz, 
      Austria. Electronic address: ute.panzenboeck@medunigraz.at.
LA  - eng
GR  - W 1226/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170314
PL  - Netherlands
TA  - Biochim Biophys Acta Mol Cell Biol Lipids
JT  - Biochimica et biophysica acta. Molecular and cell biology of lipids
JID - 101731727
RN  - 0 (ATP Binding Cassette Transporter 1)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
RN  - 0 (Apolipoproteins)
RN  - 0 (Liver X Receptors)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - ATP Binding Cassette Transporter 1/metabolism
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 1/genetics/*metabolism
MH  - Animals
MH  - Apolipoproteins/genetics/*metabolism
MH  - Biological Transport, Active/physiology
MH  - Blood-Brain Barrier/*metabolism
MH  - Cell Membrane/genetics/*metabolism
MH  - Cholesterol/genetics/*metabolism
MH  - Liver X Receptors/genetics/metabolism
MH  - *Models, Biological
MH  - Swine
OTO - NOTNLM
OT  - Cerebral cholesterol homeostasis
OT  - Endothelial cells
OT  - HDL
OT  - Liver-X receptors
OT  - Oxysterols
EDAT- 2017/03/21 06:00
MHDA- 2017/08/15 06:00
CRDT- 2017/03/19 06:00
PHST- 2016/11/10 00:00 [received]
PHST- 2017/03/07 00:00 [revised]
PHST- 2017/03/12 00:00 [accepted]
PHST- 2017/03/21 06:00 [pubmed]
PHST- 2017/08/15 06:00 [medline]
PHST- 2017/03/19 06:00 [entrez]
AID - S1388-1981(17)30051-3 [pii]
AID - 10.1016/j.bbalip.2017.03.003 [doi]
PST - ppublish
SO  - Biochim Biophys Acta Mol Cell Biol Lipids. 2017 Jun;1862(6):573-588. doi: 
      10.1016/j.bbalip.2017.03.003. Epub 2017 Mar 14.