Role of lipoproteins in the delivery of lipids to axons during axonal regeneration
Role of lipoproteins in the delivery of lipids to axons during axonal regeneration
复制标题
DOI：
10.1074/jbc.272.49.30766
复制
发表时间：
1997-12-05
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;Rusiñol, AE;Vance, JE
神经纤维的伸长涉及脂质向生长的轴突的输入。由于细胞体通常距离再生尖端很远，因此已经提出了脂质的替代来源。我们先前证明了磷脂酰胆碱的轴突合成是轴突生长所必需的（波塞德查维斯，E.，万斯，D. E、康珀诺河B。和万斯，J.E.（1995）J. Cell Biol，128，913-918;波塞德查维斯，E.，万斯，D. E、康珀诺河B。和万斯，J.E.（1995）Biochem，J.312，411-417）。相反，胆固醇不在轴突中产生。我们现在表明，当隔室培养的大鼠交感神经元与普伐他汀，在没有外源性提供的脂质，胆固醇合成被抑制和轴突生长受损。将胆固醇添加到用这种抑制剂处理的神经元的轴突或细胞体中，恢复正常的轴突伸长。同样，通过脂蛋白提供胆固醇可以恢复正常的轴突生长。相反，当轴突磷脂酰胆碱合成被抑制时，脂蛋白不能为轴突提供足够的磷脂酰胆碱用于正常伸长。因此，我们的研究支持这样的观点，即在轴突再生过程中，脂蛋白可以被轴突从微环境中摄取，并提供足够的胆固醇，但不是磷脂酰胆碱，用于生长。我们还表明，脂蛋白内的apoE和apoA-I都不是轴突生长所必需的。
Nerve fiber elongation involves the input of lipids to the growing axons. Since cell bodies are often a great distance from the regenerating tips, alternative sources of lipids have been proposed. We previously demonstrated that axonal synthesis of phosphatidylcholine is required for axonal growth (Posse de Chaves, E., Vance, D. E., Campenot, R. B. and Vance, J. E. (1995) J. Cell Biol, 128, 913-918; Posse de Chaves, E., Vance, D. E., Campenot, R. B. and Vance, J. E. (1995) Biochem, J. 312, 411-417), In contrast, cholesterol is not made in axons. We now show that when compartmented cultures of rat sympathetic neurons are incubated with pravastatin, in the absence of exogenously supplied lipids, cholesterol synthesis is inhibited and axonal growth is impaired. The addition of cholesterol to the axons or cell bodies of neurons treated with this inhibitor restores normal axonal elongation. Similarly, a supply of cholesterol via lipoproteins restores normal axonal growth. In contrast, lipoproteins do not provide axons with sufficient phosphatidylcholine for normal elongation when axonal phosphatidylcholine synthesis is inhibited. Thus, our studies support the idea that during axonal regeneration lipoproteins can be taken up by axons from the microenvironment and supply sufficient cholesterol, but not phosphatidylcholine, for growth, We also show that neither apoE nor apoA-I within the lipoproteins is essential for axonal growth.