Modulation of HepG2 cell net apolipoprotein B secretion by the citrus polymethoxyflavone, tangeretin
Modulation of HepG2 cell net apolipoprotein B secretion by the citrus polymethoxyflavone, tangeretin
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DOI：
10.1007/s11745-004-1212-8
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发表时间：
2004-02-01
期刊：
影响因子：
1.9
通讯作者：
Theriault, AG
中科院分区：
文献类型：
--
作者：
Kurowska, EM;Manthey, JA;Theriault, AG
本研究的目的是研究柑橘黄酮，多甲氧基化的柑橘类水果黄酮，对载脂蛋白B（apoB）和脂质代谢的调节人肝癌细胞株HepG 2的作用。在与72.8 μ M橘子素孵育的细胞中观察到的apoB分泌的显著减少是快速的、apoB特异性的且部分可逆的。在富含脂质的条件下也观察到这种减少，并且发现对新生apoB的蛋白酶体降解不敏感。我们通过检查脂质合成和质量来跟踪我们的研究。细胞暴露于72.8 μ M橘子素24小时，胆固醇酯、游离胆固醇和TAG的细胞内合成分别减少82%、45%和64%;橘子素还使细胞TAG的质量减少37%。橘子皮素诱导的TAG合成和质量抑制与DAG酰基转移酶（与对照组相比高达-39.0 +/-3.0%）和微粒体甘油三酯转移蛋白（与对照组相比高达-35.5 +/-2.5%）的活性降低相关。还发现橘子素激活过氧化物酶体增殖物激活受体，这是一种对FA氧化和TAG可用性具有积极调节影响的转录因子（与对照相比增加高达36%）。这些数据表明，柑橘素通过多种机制调节含载脂蛋白B的脂蛋白代谢。
The purpose of the present study was to examine the role of tangeretin, a polymethoxylated flavone from citrus fruits, on the regulation of apolipoprotein B (apoB) and lipid metabolism in the human hepatoma cell-line HepG2. The marked reduction in apoB secretion observed in cells incubated with 72.8 muM tangeretin was rapid, apoB-specific, and partly reversible. The reduction also was observed under lipid-rich conditions and found to be insensitive to proteasomal degradation of nascent apoB. We followed our study by examining lipid synthesis and mass. A 24-h exposure of cells to 72.8 muM tangeretin decreased intracellular synthesis of cholesteryl esters, free cholesterol, and TAG by 82, 45, and 64%, respectively; tangeretin also reduced the mass of cellular TAG by 37%. The tangeretin-induced suppression of TAG synthesis and mass were associated with decreased activities of DAG acyltransferase (up to -39.0 +/- 3.0% vs. control) and microsomal triglyceride transfer protein (up to -35.5 +/- 2.5% vs. control). Tangeretin was also found to activate the peroxisome proliferator-activated receptor, a transcription actor with a positive regulatory impact on FA oxidation and TAG availability (up to 36% increase vs. control). The data suggest that tangeretin modulates apoB-containing lipoprotein metabolism through multiple mechanisms.