Berberine-induced inhibition of adipocyte enhancer-binding protein 1 attenuates oxidized low-density lipoprotein accumulation and foam cell formation in phorbol 12-myristate 13-acetate-induced macrophages.
The phagocytosis of oxidized low-density lipoprotein (oxLDL) by monocyte-derived macrophages and the subsequent differentiation of macrophages into foam cells are the key steps in atherogenesis. Scavenger receptors, such as CD36 and lectin-like low-density lipoprotein receptor 1 (LOX-1), are responsible for the uptake of oxLDL. Adipocyte enhancer-binding protein 1 (AEBP1) regulates many key genes associated with intracellular cholesterol efflux. The present study investigated the function of berberine, a compound isolated from Rhizoma coptidis, on foam cell formation, and explored the possible underlying mechanism. We found that berberine inhibited the oxLDL uptake of macrophages and reduced foam cell formation in a dose-dependent manner. Moreover, AEBP1 expression in macrophages increased and decreased after oxLDL and berberine treatments in a dose-dependent manner, respectively. Berberine reduced the expression of scavenger receptors CD36 and LOX-1, but did not affect the expression of CD68 in oxLDL-stimulated macrophages. Overall, berberine reduced foam cell formation by a dual mechanism, which decreased oxLDL internalization via the suppression of CD36 and LOX-1, and increased cholesterol efflux by inhibiting AEBP1 expression in macrophages.
Department of Cardiology of Cardiac Center, The First Affiliated Hospital of Wenzhou Medical College, 2 Fuxue Road, WenZhou, ZheJiang 325000, PR China. susiehzq@yahoo.cn
Zhouqing
Z
Huang
Fengquan
F
Dong
Sheng
S
Li
Maoping
M
Chu
Hao
H
Zhou
Zhongqiu
Z
Lu
Weijian
W
Huang
D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001599:Berberine / Q000494:pharmacology*; D018955:CD36 Antigens / Q000378:metabolism; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002460:Cell Line; D002788:Cholesterol Esters / Q000378:metabolism; D005487:Foam Cells / Q000187:drug effects* / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D012097:Repressor Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001599:Berberine; D018955:CD36 Antigens; D002268:Carboxypeptidases; D002788:Cholesterol Esters; D008077:Lipoproteins, LDL; D012097:Repressor Proteins; D051127:Scavenger Receptors, Class E; D013755:Tetradecanoylphorbol Acetate; C484818:AEBP1 protein, human; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C495137:OLR1 protein, human; C099252:oxidized low density lipoprotein