Huang Y, Hui D Y
Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, OH 45267-0529.
Biochim Biophys Acta. 1994 Oct 6;1214(3):317-22. doi: 10.1016/0005-2760(94)90079-5.
This study used the rat pancreatoma AR42J cells as a model to determine the effects of cholesterol on cholesterol esterase biosynthesis. Incubation of AR42J cells with low-density lipoproteins (LDL) or with the cholesterol-induced beta-very-low-density lipoproteins did not result in changes in cellular cholesterol levels. These cholesterol-rich lipoproteins also had no effect on cholesterol esterase biosynthesis by the AR42J cells. Cellular cholesterol level was found to increase by approx. 2-fold after incubating the AR42J cells with cationized-LDL. The increase in cellular cholesterol level resulted in a higher level of cholesterol esterase secreted into the culture medium. The increased cellular cholesterol also resulted in higher amounts of cholesterol esterase detected in the AR42J cell lysate. The increase in cholesterol esterase level corresponded to a cholesterol-induced increase in steady-state level of cholesterol esterase mRNA. The results of this study, and our previous observation of post-transcriptional activation of cholesterol esterase induced by intestinal hormones (Huang, Y. and Hui, D.Y. (1991) J. Biol. Chem. 266, 6720-6725), suggested that cholesterol esterase biosynthesis may be regulated by transcriptional and translational mechanisms in response to hormonal and nutrient stimulation of the pancreatic acinar cells. Additionally, the regulation of cholesterol esterase biosynthesis by cholesterol loading of the pancreatic cells suggested a possible role of this enzyme in cholesterol metabolism.
本研究以大鼠胰腺瘤AR42J细胞为模型，以确定胆固醇对胆固醇酯酶生物合成的影响。用低密度脂蛋白（LDL）或胆固醇诱导的β-极低密度脂蛋白孵育AR42J细胞，并不会导致细胞胆固醇水平发生变化。这些富含胆固醇的脂蛋白对AR42J细胞的胆固醇酯酶生物合成也没有影响。在用阳离子化LDL孵育AR42J细胞后，发现细胞胆固醇水平大约增加了2倍。细胞胆固醇水平的升高导致分泌到培养基中的胆固醇酯酶水平升高。细胞内胆固醇增加还导致在AR42J细胞裂解物中检测到更多的胆固醇酯酶。胆固醇酯酶水平的升高与胆固醇诱导的胆固醇酯酶mRNA稳态水平的增加相对应。本研究结果以及我们之前观察到的肠道激素诱导胆固醇酯酶的转录后激活（Huang, Y.和Hui, D.Y.（1991年）《生物化学杂志》266, 6720 - 6725）表明，胆固醇酯酶的生物合成可能受转录和翻译机制调控，以响应胰腺腺泡细胞的激素和营养刺激。此外，胰腺细胞的胆固醇负载对胆固醇酯酶生物合成的调节表明该酶在胆固醇代谢中可能发挥作用。
