LIPOPROTEIN UPTAKE BY NEURONAL GROWTH CONES INVITRO
LIPOPROTEIN UPTAKE BY NEURONAL GROWTH CONES INVITRO
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DOI：
10.1126/science.3576212
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发表时间：
1987-05-22
期刊：
影响因子：
56.9
通讯作者：
MAHLEY, RW
中科院分区：
文献类型：
--
作者：
IGNATIUS, MJ;SHOOTER, EM;MAHLEY, RW
巨噬细胞迅速进入损伤的周围神经，合成并分泌大量载脂蛋白E。这种蛋白质可能参与脂质（包括变性过程中释放的胆固醇）向再生轴突的再分配。为了验证这一假设，载脂蛋白E相关的脂质颗粒从受损的大鼠坐骨神经和血浆中的载脂蛋白E-脂蛋白段释放，以确定是否发芽的神经突，特别是他们的生长锥，拥有脂蛋白受体。嗜铬细胞瘤（PC 12）细胞，它可以在体外刺激产生神经突起，被用作模型系统。含有载脂蛋白E的脂质颗粒和脂蛋白，已被标记的荧光染料，内化的神经突和它们的生长锥;未代谢的染料似乎是本地化的溶酶体。在生长锥中的快速积累排除了荧光颗粒从PC 12细胞体顺行运输的可能性。因此，受体介导的脂蛋白摄取由载脂蛋白B、E（LDL）（低密度脂蛋白）受体进行，并且在再生的外周神经中，载脂蛋白E可将脂质递送至神经突及其生长锥以进行膜生物合成。
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.