[Effects of oxidized low-density lipoprotein on cholesterol efflux in 3T3-L1 cells].
OBJECTIVE
To explore whether oxidized low-density lipoprotein (ox-LDL) can stimulate the cholesterol efflux in fully differentiated 3T3-L1 cells and the possible mechanism.


METHODS
Fully differentiated 3T3-L1 cells were incubated in the medium containing various concentrations of ox-LDL ( 0 to 50 microg/mL) for 8 or 24 hours. 22(R)-Hydroxycholesterol (10 micromol/L) was exposed to preconditioned adipocytes with 25 microg/mL ox-LDL for 24 hours. Reverse transcription polymerase chain reaction (RT-PCR) was used to evaluate ATP binding cassette transporter A1 (ABCA1), scavenger receptor class B type I (SR-BI), and liver X receptor alpha (LXRalpha) mRNA expression. Cholesterol efflux mediated by apolipoprotein A-I (apoA-I) was determined using liquid scintillator.


RESULTS
Low levels (12.5-25 microg/mL) of ox-LDL could increase cholesterol efflux via the enhancement of ABCA1 pathway and SR-BI expression, whereas the higher concentration (50 microg/mL) could not. In adipocytes preincubated with 25 microg/mL ox-LDL for 24 hours, 22(R)-hydroxycholesterol could increase ABCA1 and LXRalpha mRNA and apoA-I-mediated cholesterol efflux, but had no effect on the SR-BI mRNA expression.


CONCLUSIONS
Low levels of ox-LDL may enhance the LXRalpha-ABCA1-apoA-I pathway in adipocytes, up-regulate SR-BI mRNA expression, and then increase the cholesterol efflux. This new effect of ox-LDL will not only make contribution to cholesterol homeostasis in adipocytes, but also be potentially atheroprotective.
Yu
Bi-Lian
BL
Department of Cardiology, Second Xiangya Hospital, Central South University, Changsha 410011, China.
Zhao
Shui-Ping
SP
Xie
Xiang-Zhu
XZ
Dong
Shao-Zhuang
SZ
Dong
Jing
J
D041721:3T3-L1 Cells; D064286:ATP Binding Cassette Transporter 1 / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D050356:Lipid Metabolism; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D000071518:Liver X Receptors; D051379:Mice; D057093:Orphan Nuclear Receptors / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000378:metabolism
D064286:ATP Binding Cassette Transporter 1; D002784:Cholesterol; D008077:Lipoproteins, LDL; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D051122:Scavenger Receptors, Class B; C577833:Abca1 protein, mouse; C000605214:Nr1h3 protein, mouse; C454739:Scarb1 protein, mouse; C099252:oxidized low density lipoprotein