PMID- 25512280
OWN - NLM
STAT- MEDLINE
DCOM- 20150908
LR  - 20181202
IS  - 1671-167X (Print)
IS  - 1671-167X (Linking)
VI  - 46
IP  - 6
DP  - 2014 Dec 18
TI  - [Decline of ATP-binding cassette transporter G1 expressions with a liver X 
      receptor-independent pathway in patients with type 2 diabetes].
PG  - 899-905
AB  - OBJECTIVE: To examine the cholesterol efflux and the expressions of ATP-binding 
      cassette transporter G1 (ABCG1) in macrophages of diabetic patients and the roles 
      of liver-X receptor (LXR) in regulation of ABCG1 expressions. METHODS: Blood was 
      collected from patients with type 2 diabetes mellitus and healthy controls. The 
      peripheral blood monocytes were differentiated into macrophages with macrophage 
      colony stimulating factor (M-CSF). The cells were radio labeled with [(3)H] 
      cholesterol and were performed with cholesterol efflux assays. Quantitative 
      real-time PCR (qRT PCR) and Western blot were performed to measure the mRNA and 
      protein expressions of ABCA1 and ABCG1. To test the effects of LXR on ABCG1 
      expressions, inhibition of LXRalpha and LXRbeta by siRNA were performed. The DNA-protein 
      complex of LXR and LXR element (LXRE) located in the promoter region of ABCG1 
      gene were detected with electrophery mobility supershift assay (EMSA). RESULTS: 
      Macrophage ABCG1 expressions and high-density lipoprotein (HDL) induced 
      cholesterol efflux were significantly reduced (19.0%+/-1.2% vs. 12.8%+/-3.6%, 
      t=2.532, P=0.016) in the diabetic subjects whereas ABCA1 expressions and 
      apolipoprotein A1 (ApoA1) induced cholesterol efflux were comparable (12.0%+/-1.2% 
      vs. 10.2%+/-2.3%, t=1.771, P=0.109) between the diabetic patients and healthy 
      subjects. The mRNA expressions of LXRalpha and LXRbeta had no changes between the 
      diabetes subjects and healthy controls (t=1.025, P=0.315; t=-0.531, P=0.600). The 
      LXR-LXRE DNA-protein complex detected by EMSA were also similar between the 
      diabetes subjects and healthy controls (t=1.483, P=0.164). Moreover, ABCG1 
      expressions were not altered by inhibition of LXRalpha/beta siRNA (t=2.143, P=0.061). 
      CONCLUSION: Our data indicated that expression of ABCG1 and HDL induced 
      cholesterol efflux were reduced in type 2 diabetic patients. However, the LXR 
      mRNA expression and binding complex of LXR and ABCG1 promoter were not changed. 
      The impairment of cholesterol efflux and ABCG1 gene expressions might be 
      regulated via an LXR-independent pathway.
FAU - Wang, H J
AU  - Wang HJ
AD  - Department of Cardiology, Peking Jishuitan Hospital, Beijing 100035, China.
FAU - Zhao, X S
AU  - Zhao XS
AD  - Department of Cardiology, Peking Jishuitan Hospital, Beijing 100035, China.
FAU - Sun, H Y
AU  - Sun HY
AD  - Department of Cardiology, Peking Jishuitan Hospital, Beijing 100035, China.
FAU - Chen, L F
AU  - Chen LF
AD  - Department of Cardiology, Peking Union Medical College Hospital, Beijing 100730, 
      China.
FAU - Yan, X W
AU  - Yan XW
AD  - Department of Cardiology, Peking Union Medical College Hospital, Beijing 100730, 
      China.
LA  - chi
PT  - Journal Article
PL  - China
TA  - Beijing Da Xue Xue Bao Yi Xue Ban
JT  - Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health 
      sciences
JID - 101125284
RN  - 0 (ABCG1 protein, human)
RN  - 0 (ATP Binding Cassette Transporter, Subfamily G, Member 1)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Liver X Receptors)
RN  - 0 (NR1H3 protein, human)
RN  - 0 (Orphan Nuclear Receptors)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - ATP Binding Cassette Transporter, Subfamily G, Member 1
MH  - ATP-Binding Cassette Transporters/*metabolism
MH  - Cells, Cultured
MH  - Cholesterol/metabolism
MH  - Diabetes Mellitus, Type 2/*metabolism
MH  - Gene Expression
MH  - Humans
MH  - Liver X Receptors
MH  - Macrophages/*metabolism
MH  - Orphan Nuclear Receptors/*metabolism
MH  - Real-Time Polymerase Chain Reaction
EDAT- 2014/12/17 06:00
MHDA- 2015/09/09 06:00
CRDT- 2014/12/17 06:00
PHST- 2014/12/17 06:00 [entrez]
PHST- 2014/12/17 06:00 [pubmed]
PHST- 2015/09/09 06:00 [medline]
PST - ppublish
SO  - Beijing Da Xue Xue Bao Yi Xue Ban. 2014 Dec 18;46(6):899-905.