Uptake of lipoproteins for axonal growth of sympathetic neurons
Uptake of lipoproteins for axonal growth of sympathetic neurons
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DOI：
10.1074/jbc.275.26.19883
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发表时间：
2000-06-30
影响因子：
4.8
通讯作者：
Vance, JE
中科院分区：
文献类型：
--
作者：
de Chaves, EIP;Vance, DE;Vance, JE
在损伤的周围神经中，来自轴突和髓磷脂分解的脂蛋白被认为向再生的轴突提供胆固醇。我们使用大鼠交感神经元的隔室培养物来研究脂蛋白中的脂质对轴突伸长的利用。来自人低密度脂蛋白（LDL）和高密度脂蛋白（HDL）的脂质和蛋白质被远端轴突摄取并转运到细胞体，而细胞体/近端轴突仅内化来自LDL的这些组分，而不是HDL。与这些观察结果一致，轴突生长的损害，诱导抑制胆固醇合成，逆转时，LDL或HDL添加到远端轴突或当LDL，但不是HDL，添加到细胞体。LDL受体（LDLRs）和LR 7/8B（apoER 2）存在于细胞体/近端轴突和远端轴突中，LDLRs在前者中更丰富。胆固醇生物合成的抑制增加了细胞体/近端轴突中的LDLR表达，但未增加远端轴突中的LDLR表达。LR 11（SorLA）仅限于细胞体/近端轴突，而在远端轴突中检测不到。在交感神经元中既未检测到LDL受体相关蛋白，也未检测到HDL受体SR-B1。这些研究第一次证明了脂质是由交感神经元从脂蛋白中摄取的，用于轴突再生。
Lipoproteins originating from axon and myelin breakdown in injured peripheral nerves are believed to supply cholesterol to regenerating axons. We have used compartmented cultures of rat sympathetic neurons to investigate the utilization of lipids from lipoproteins for axon elongation. Lipids and proteins from human low density lipoproteins (LDL) and high density lipoproteins (HDL) were taken up by distal axons and transported to cell bodies, whereas cell bodies/proximal axons internalized these components from only LDL, not HDL. Consistent with these observations, the impairment of axonal growth, induced by inhibition of cholesterol synthesis, was reversed when LDL or HDL were added to distal axons or when LDL, but not HDL, were added to cell bodies. LDL receptors (LDLRs) and LR7/8B (apoER2) were present in cell bodies/proximal axons and distal axons, with LDLRs being more abundant in the former. Inhibition of cholesterol biosynthesis increased LDLR expression in cell bodies/proximal axons but not distal axons. LR11 (SorLA) was restricted to cell bodies/proximal axons and was undetectable in distal axons, Neither the LDL receptor-related protein nor the HDL receptor, SR-B1, was detected in sympathetic neurons. These studies demonstrate for the first time that lipids are taken up from lipoproteins by sympathetic neurons for use in axonal regeneration.