Oxidized low-density lipoprotein activates adipophilin through ERK1/2 signal pathway in RAW264.7 cells.
It has been reported that oxidized low-density lipoprotein (Ox-LDL) can increase the expression of adipophilin. However, the detailed mechanisms are not fully understood. The aim of this study was to investigate the mechanism of Ox-LDL on adipophilin expression and the intracellular lipid droplet accumulation. A mouse macrophage-like cell line, RAW264.7, was used throughout, and it was found that Ox-LDL induced adipophilin expression in a dose-dependent manner. Moreover, Ox-LDL induced peroxisome proliferator-activated receptor-gamma (PPARgamma) expression and PPARgamma-specific inhibitor T0070907 abrogated Ox-LDL-induced adipophilin expression, but specific agonist GW1929 not. Furthermore, Ox-LDL induced phosphorylation of ERK1/2, and ERK1/2-specific inhibition by PD98059 suppressed the Ox-LDL-induced PPARgamma and adipophilin expression. The results showed that ERK1/2 or PPARgamma-specific inhibition decreased the amounts of intracellular lipid droplets. Meanwhile, the PPARgamma-specific agonist increased intracellular lipid droplets. These results suggested that Ox-LDL-induced increase in adipophilin level via ERK1/2 activation is one of the mechanisms of inducing greater amounts of intracellular lipid droplets in RAW264.7 cells, which indicated that adipophilin is involved in atherosclerotic progression.
Liu
Qingnan
Q
Institute of Cardiovascular Disease, University of South China, Hengyang, China.
Dai
Zhibing
Z
Liu
Zhiqiang
Z
Liu
Xiaohui
X
Tang
Chaoke
C
Wang
Zuo
Z
Yi
Guanghui
G
Liu
Lushan
L
Jiang
Zhisheng
Z
Yang
Yongzong
Y
Yuan
Zhonghua
Z
D000818:Animals; D001549:Benzamides / Q000494:pharmacology; D015153:Blotting, Western; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D005419:Flavonoids / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000032:analysis; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D000070780:Perilipin-2; D010766:Phosphorylation / Q000187:drug effects; D011725:Pyridines / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors
D001549:Benzamides; D005419:Flavonoids; D008055:Lipids; D008077:Lipoproteins, LDL; D008565:Membrane Proteins; C000602982:PLIN2 protein, human; D047495:PPAR gamma; D010455:Peptides; D000070780:Perilipin-2; C000602983:Plin2 protein, mouse; D011725:Pyridines; C458508:T 0070907; C099252:oxidized low density lipoprotein; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one