LXR agonist increases apoE secretion from HepG2 spheroid, together with an increased production of VLDL and apoE-rich large HDL.
LXR agonist increases apoE secretion from HepG2 spheroid, together with an increased production of VLDL and apoE-rich large HDL.
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DOI：
10.1186/1476-511x-10-134
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发表时间：
2011-08-05
影响因子：
4.5
通讯作者：
Tsukamoto K
中科院分区：
文献类型：
--
作者：
Kurano M;Iso-O N;Hara M;Ishizaka N;Moriya K;Koike K;Tsukamoto K
肝脏apoE基因的生理调节尚未阐明，尽管已知脂肪细胞和巨噬细胞中apoE的表达受LXR调节。我们研究了TO 901317（一种LXR激动剂）对肝apoE产生的影响，使用以球状体形式培养的HepG 2细胞，已知其比单层培养中的HepG 2细胞分化更大。在藻酸盐珠中制备球形HepG 2细胞。与单层HepG 2细胞相比，球形HepG 2细胞白蛋白、apoE和apoA-I的分泌量显著增加，并伴随apoE和apoA-I mRNA水平的增加。包括LXRα在内的几种核受体也在球状体HepG 2细胞的核组分中变得丰富。用TO 901317处理显著增加球状体HepG 2细胞的apoE蛋白分泌，这也与apoE mRNA表达的增加相关。用FPLC分离培养基显示，即使在低浓度的TO 901317下，富含apoE的大HDL颗粒的产生也增加，并且在较高浓度的TO 901317下，VLDL颗粒的产生也增加。LXR激活增强了肝脏apoE的表达，同时改变了分化的肝细胞衍生细胞产生的脂蛋白颗粒。HepG 2球状体可能作为一个很好的模型，分化良好的人肝细胞的肝脏脂质代谢的未来调查。
The physiological regulation of hepatic apoE gene has not been clarified, although the expression of apoE in adipocytes and macrophages has been known to be regulated by LXR. We investigated the effect of TO901317, a LXR agonist, on hepatic apoE production utilizing HepG2 cells cultured in spheroid form, known to be more differentiated than HepG2 cells in monolayer culture. Spheroid HepG2 cells were prepared in alginate-beads. The secretions of albumin, apoE and apoA-I from spheroid HepG2 cells were significantly increased compared to those from monolayer HepG2 cells, and these increases were accompanied by increased mRNA levels of apoE and apoA-I. Several nuclear receptors including LXRα also became abundant in nuclear fractions in spheroid HepG2 cells. Treatment with TO901317 significantly increased apoE protein secretion from spheroid HepG2 cells, which was also associated with the increased expression of apoE mRNA. Separation of the media with FPLC revealed that the production of apoE-rich large HDL particles were enhanced even at low concentration of TO901317, and at higher concentration of TO901317, production of VLDL particles increased as well. LXR activation enhanced the expression of hepatic apoE, together with the alteration of lipoprotein particles produced from the differentiated hepatocyte-derived cells. HepG2 spheroids might serve as a good model of well-differentiated human hepatocytes for future investigations of hepatic lipid metabolism.