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标题：Rapid initial removal of chylomicron remnants by the mouse liver does not require hepatically localized apolipoprotein E
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作者：Kenneth C-W. Yu ; Yuan Jiang ; Wei Chen 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2000
卷号：41
期号：11
页码：1715-1727
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Apolipoprotein E (apoE) is a ligand for the low density lipoprotein receptor (LDLR) and the low density lipoprotein receptor-related protein (LRP). The aim of the present study was to clarify the role of hepatically localized apoE in the rapid initial removal of chylomicron remnants by using the isolated perfused liver. Radiolabeled chylomicron remnants were perfused in a single nonrecirculating pass into the livers of C57BL/6J (wild-type) mice, apoE-knockout mice, and apoE/LDLR-knockout mice for a period of 20 min. Aliquots of the perfusate leaving the liver were collected at regular intervals and the rate of removal of radioactivity was determined. At a trace concentration of chylomicron remnants (0.05 μg of protein per ml), wild-type mouse livers removed at a steady state of 50–55% of total chylomicron remnants perfused per pass; livers from apoE-knockout mice had the same capacity as wild-type mouse livers. When the concentration of remnants was increased to 12 μg of protein per ml, a level at which it has been shown that LDL receptor and LRP are near saturation, the capacity of the wild-type mouse livers to remove chylomicron remnants was decreased to 10–25% per pass, confirming that the removal mechanisms were nearing saturation. However, instead of finding a greater reduction in the removal rates or impairment in chylomicron remnant removal, livers from apoE-knockout mice were just as efficient as those from wild-type mice in removing remnants. Livers of mice that lacked both apoE and the LDLR also had a similar rate of removal at relatively low remnant concentrations (0.05–0.5 μg/ml), but had reduced capacity in removing remnants at a relatively high concentration (4–12 μg/ml) of chylomicron remnants (~20% per pass). The rate of removal at these concentrations, however, was similar to that attributed to the LRP in previous studies. Chylomicron remnants, whose apolipoproteins were disrupted by trypsinization, were removed at a normal rate by wild-type mouse livers but there was almost no removal by apoE-knockout mouse livers. At higher concentrations, however, the removal of apolipoprotein-disrupted chylomicron remnants was decreased. Our present findings do not support the hypothesis that hepatically localized apoE is a critical factor in the rapid initial removal of chylomicron remnants by either of the major pathways but do suggest that hepatically localized apoE can be added to lipoproteins to accelerate their uptake, although this process may have a limited capacity to compensate for apoE deficiency on lipoproteins. —Yu, K. C-W., Y. Jiang, W. Chen, and A. D. Cooper. Rapid initial removal of chylomicron remnants by the mouse liver does not require hepatically localized apolipoprotein E. J. Lipid Res. 2000. 41: 1715–1727.
关键词：chylomicron remnants ; low density lipoprotein receptor ; low density lipoprotein receptor-related protein ; atherosclerosis