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ABCA1 upregulating apolipoproein M expression mediates via the RXR/LXR pathway in HepG2 cells

Di, Dongmei; Wang, Zongchun; Liu, Yang; Luo, Guanghua; Shi, Yuanping; Berggren Söderlund, Maria LU ; Nilsson-Ehle, Peter LU ; Zhang, Xiaoying and Xu, Ning LU (2012) In Biochemical and Biophysical Research Communications 421(1). p.152-156
Abstract
We have previously reported that liver X receptor (LXR) agonist, TO901317, could significantly inhibit hepatic apolipoprotein M (apoM) expression. It has been reported that TO901317 could activate the ATP-binding cassette transporter A1 (ABCA1) that mediates cholesterol efflux to the lipid-poor apoA1, which is an essential step for the high-density lipoprotein (HDL) formation. It is unknown if ABCA1 may regulate hepatic apoM expression. In the present study, HepG2 cells were cultured with the synthetic LXR agonists, TO901317 or GW3965 in the presence or absence of ABCA1 antagonist, disodium 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS). The mRNA levels of ABCA1, apoM and liver receptor homolog-1 (LRH-1) determined by the real-time... (More)
We have previously reported that liver X receptor (LXR) agonist, TO901317, could significantly inhibit hepatic apolipoprotein M (apoM) expression. It has been reported that TO901317 could activate the ATP-binding cassette transporter A1 (ABCA1) that mediates cholesterol efflux to the lipid-poor apoA1, which is an essential step for the high-density lipoprotein (HDL) formation. It is unknown if ABCA1 may regulate hepatic apoM expression. In the present study, HepG2 cells were cultured with the synthetic LXR agonists, TO901317 or GW3965 in the presence or absence of ABCA1 antagonist, disodium 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS). The mRNA levels of ABCA1, apoM and liver receptor homolog-1 (LRH-1) determined by the real-time RT-PCR. It demonstrated that both TO901317 and GW3965 could significantly enhance ABCA1 expression, and simultaneously, inhibit LRH1 expression. However, TO901317 alone could significantly inhibit apoM expression, while GW3965 alone did not influence apoM expression. ABCA1 antagonist, DIDS, have no effects on GW3965 induced upregulation of ABCA1 and downregulation of LRH1. However, apoM mRNA level was significantly decreased when the cells cultured with GW3965 together with DIDS. The present study demonstrated that apoM expression could be elevated by ABCA1 via the RXR/LXR pathway and LRH1 does not involve in the regulation of apoM by the activation of ABCA1, although the direct regulative pathway(s) between ABCA1 and apoM gene is still unknown yet. The detailed mechanism needs further investigation. (C) 2012 Elsevier Inc. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
ATP-binding cassette transporters, Apolipoprotein M, Liver receptor, homolog-1, Liver X receptor
in
Biochemical and Biophysical Research Communications
volume
421
issue
1
pages
152 - 156
publisher
Elsevier
external identifiers
  • wos:000304501400027
  • scopus:84860332644
ISSN
1090-2104
DOI
10.1016/j.bbrc.2012.04.022
language
English
LU publication?
yes
id
87e906b6-3b44-414e-bec0-f7c04e086938 (old id 2911692)
date added to LUP
2012-08-01 09:47:51
date last changed
2017-07-02 03:55:13
@article{87e906b6-3b44-414e-bec0-f7c04e086938,
  abstract     = {We have previously reported that liver X receptor (LXR) agonist, TO901317, could significantly inhibit hepatic apolipoprotein M (apoM) expression. It has been reported that TO901317 could activate the ATP-binding cassette transporter A1 (ABCA1) that mediates cholesterol efflux to the lipid-poor apoA1, which is an essential step for the high-density lipoprotein (HDL) formation. It is unknown if ABCA1 may regulate hepatic apoM expression. In the present study, HepG2 cells were cultured with the synthetic LXR agonists, TO901317 or GW3965 in the presence or absence of ABCA1 antagonist, disodium 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS). The mRNA levels of ABCA1, apoM and liver receptor homolog-1 (LRH-1) determined by the real-time RT-PCR. It demonstrated that both TO901317 and GW3965 could significantly enhance ABCA1 expression, and simultaneously, inhibit LRH1 expression. However, TO901317 alone could significantly inhibit apoM expression, while GW3965 alone did not influence apoM expression. ABCA1 antagonist, DIDS, have no effects on GW3965 induced upregulation of ABCA1 and downregulation of LRH1. However, apoM mRNA level was significantly decreased when the cells cultured with GW3965 together with DIDS. The present study demonstrated that apoM expression could be elevated by ABCA1 via the RXR/LXR pathway and LRH1 does not involve in the regulation of apoM by the activation of ABCA1, although the direct regulative pathway(s) between ABCA1 and apoM gene is still unknown yet. The detailed mechanism needs further investigation. (C) 2012 Elsevier Inc. All rights reserved.},
  author       = {Di, Dongmei and Wang, Zongchun and Liu, Yang and Luo, Guanghua and Shi, Yuanping and Berggren Söderlund, Maria and Nilsson-Ehle, Peter and Zhang, Xiaoying and Xu, Ning},
  issn         = {1090-2104},
  keyword      = {ATP-binding cassette transporters,Apolipoprotein M,Liver receptor,homolog-1,Liver X receptor},
  language     = {eng},
  number       = {1},
  pages        = {152--156},
  publisher    = {Elsevier},
  series       = {Biochemical and Biophysical Research Communications},
  title        = {ABCA1 upregulating apolipoproein M expression mediates via the RXR/LXR pathway in HepG2 cells},
  url          = {http://dx.doi.org/10.1016/j.bbrc.2012.04.022},
  volume       = {421},
  year         = {2012},
}