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

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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; Nilsson-Ehle, Peter; Zhang, Xiaoying; Xu, Ning.

I: Biochemical and Biophysical Research Communications, Vol. 421, Nr. 1, 2012, s. 152-156.

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Di, Dongmei ; Wang, Zongchun ; Liu, Yang ; Luo, Guanghua ; Shi, Yuanping ; Berggren Söderlund, Maria ; Nilsson-Ehle, Peter ; Zhang, Xiaoying ; Xu, Ning. / ABCA1 upregulating apolipoproein M expression mediates via the RXR/LXR pathway in HepG2 cells. I: Biochemical and Biophysical Research Communications. 2012 ; Vol. 421, Nr. 1. s. 152-156.

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TY - JOUR

T1 - ABCA1 upregulating apolipoproein M expression mediates via the RXR/LXR pathway in HepG2 cells

AU - Di, Dongmei

AU - Wang, Zongchun

AU - Liu, Yang

AU - Luo, Guanghua

AU - Shi, Yuanping

AU - Berggren Söderlund, Maria

AU - Nilsson-Ehle, Peter

AU - Zhang, Xiaoying

AU - Xu, Ning

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - ATP-binding cassette transporters

KW - Apolipoprotein M

KW - Liver receptor

KW - homolog-1

KW - Liver X receptor

U2 - 10.1016/j.bbrc.2012.04.022

DO - 10.1016/j.bbrc.2012.04.022

M3 - Article

VL - 421

SP - 152

EP - 156

JO - Biochemical and Biophysical Research Communications

T2 - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

SN - 1090-2104

IS - 1

ER -