Ignatius M J, Shooter E M, Pitas R E, Mahley R W
Science. 1987 May 22;236(4804):959-62. doi: 10.1126/science.3576212.
Macrophages that rapidly enter injured peripheral nerve synthesize and secrete large quantities of apolipoprotein E. This protein may be involved in the redistribution of lipid, including cholesterol released during degeneration, to the regenerating axons. To test this postulate, apolipoprotein E-associated lipid particles released from segments of injured rat sciatic nerve and apolipoprotein E-containing lipoproteins from plasma were used to determine whether sprouting neurites, specifically their growth cones, possessed lipoprotein receptors. Pheochromocytoma (PC12) cells, which can be stimulated to produce neurites in vitro, were used as a model system. Apolipoprotein E-containing lipid particles and lipoproteins, which had been labeled with fluorescent dye, were internalized by the neurites and their growth cones; the unmetabolized dye appeared to be localized to the lysosomes. The rapid rate of accumulation in the growth cones precludes the possibility of orthograde transport of the fluorescent particles from the PC12 cell bodies. Thus, receptor-mediated lipoprotein uptake is performed by the apolipoprotein B,E(LDL) (low density lipoprotein) receptors, and in the regenerating peripheral nerve apolipoprotein E may deliver lipids to the neurites and their growth cones for membrane biosynthesis.
迅速进入受损周围神经的巨噬细胞合成并分泌大量载脂蛋白E。这种蛋白质可能参与脂质的重新分布，包括在变性过程中释放的胆固醇，将其转运至再生轴突。为了验证这一假设，研究人员利用从受伤大鼠坐骨神经节段释放的载脂蛋白E相关脂质颗粒以及血浆中含载脂蛋白E的脂蛋白，来确定发芽的神经突，特别是其生长锥，是否拥有脂蛋白受体。嗜铬细胞瘤（PC12）细胞在体外可被刺激产生神经突，被用作模型系统。用荧光染料标记的含载脂蛋白E的脂质颗粒和脂蛋白被神经突及其生长锥内化；未代谢的染料似乎定位于溶酶体。生长锥中快速的积累速率排除了荧光颗粒从PC12细胞体正向运输的可能性。因此，受体介导的脂蛋白摄取是由载脂蛋白B、E（低密度脂蛋白）受体完成的，并且在再生的周围神经中，载脂蛋白E可能将脂质递送至神经突及其生长锥以进行膜生物合成。
