Overbergh L, Lorent K, Torrekens S, Van Leuven F, Van den Berghe H
Department of Human Genetics, Katholieke Universiteit van Leuven, Belgium.
J Lipid Res. 1995 Aug;36(8):1774-86.
The expression of the proteinase inhibitors of the alpha-macroglobulin family and of their clearance receptor was analyzed in the mouse during pregnancy, embryonal development, and adolescence. In total we studied seven partners of a complicated network of interactions in proteolysis and lipid metabolism:alpha-2-macroglobulin, murinoglobulin, the alpha-2-macroglobulin receptor/lipoprotein receptor related protein, the murine equivalent of the receptor associated protein or the 44 kDa heparin binding protein, the low density lipoprotein receptor, apolipoprotein E, and lipoprotein lipase. The data demonstrate that: i) the regulation of expression of mouse tetrameric alpha-2-macroglobulin results in very constant levels, similar to alpha-2-macroglobulin in humans; ii) single chain murinoglobulin, not alpha-2-macroglobulin, is subject to regulation of expression during pregnancy, around birth, and in adolescence; iii) an important role seems implicated for the alpha-2-macroglobulin receptor in placental lipid metabolism, probably making it the most important lipoprotein receptor to supply the fetus; iv) the massive increase in apolipoprotein E synthesis in uterus and placenta accentuate the changed lipid metabolism during pregnancy to an apolipoprotein E-based uptake by the alpha-2-macroglobulin receptor/lipoprotein receptor related protein; v) the increased expression of lipoprotein lipase underlines its role in the generation of free fatty acids in uterus and placenta as another mechanism of supply, next to receptor mediated endocytosis of lipoproteins.
在小鼠的孕期、胚胎发育和青春期,对α-巨球蛋白家族蛋白酶抑制剂及其清除受体的表达进行了分析。我们总共研究了蛋白质水解和脂质代谢复杂相互作用网络中的七个成员:α-2-巨球蛋白、鼠球蛋白、α-2-巨球蛋白受体/脂蛋白受体相关蛋白、受体相关蛋白的小鼠等效物或44 kDa肝素结合蛋白、低密度脂蛋白受体、载脂蛋白E和脂蛋白脂肪酶。数据表明:i)小鼠四聚体α-2-巨球蛋白的表达调控导致其水平非常恒定,类似于人类的α-2-巨球蛋白;ii)单链鼠球蛋白而非α-2-巨球蛋白在孕期、出生前后及青春期会受到表达调控;iii)α-2-巨球蛋白受体在胎盘脂质代谢中似乎起着重要作用,可能使其成为为胎儿提供营养的最重要的脂蛋白受体;iv)子宫和胎盘中载脂蛋白E合成的大量增加,加剧了孕期脂质代谢向基于载脂蛋白E的α-2-巨球蛋白受体/脂蛋白受体相关蛋白摄取的转变;v)脂蛋白脂肪酶表达的增加突出了其在子宫和胎盘中生成游离脂肪酸的作用,这是继脂蛋白受体介导的内吞作用之后的另一种营养供应机制。