Goodrum J F, Bouldin T W, Zhang S H, Maeda N, Popko B
Brain and Development Research Center, University of North Carolina at Chapel Hill 27599.
J Neurochem. 1995 Jan;64(1):408-16. doi: 10.1046/j.1471-4159.1995.64010408.x.
Apolipoproteins have been implicated in the salvage and reutilization of myelin cholesterol during Wallerian degeneration and the subsequent nerve regeneration. Current evidence suggests that myelin cholesterol complexes with apolipoproteins E and A-I to form lipoproteins that are taken up via low-density lipoprotein receptors on myelinating Schwann cells. We recently reported, however, that apolipoprotein E is not required for nerve regeneration or reutilization of myelin cholesterol. We have now investigated nerve regeneration and the reutilization of cholesterol in mutant mice deficient in both apolipoproteins E and A-I. Morphologic examination of nerves 4 and 12 weeks after crush injury revealed that regeneration proceeded at a normal rate in the absence of these apolipoproteins. Autoradiography of regenerating nerves indicated that prelabeled myelin lipid was reutilized in the regenerating myelin. 3-Hydroxy-3-methylglutaryl-CoA reductase, the rate-limiting enzyme in cholesterol synthesis, was down-regulated in the regenerating nerves, indicative of cholesterol uptake via lipoproteins. Prelabeled myelin cholesterol was present in lipoprotein fractions isolated from crushed nerves of mutant mice. These data suggest that there is considerable redundancy in the process of cholesterol reutilization within nerve, and that apolipoproteins other than apolipoproteins E and A-I may be involved in the recycling of myelin cholesterol.
载脂蛋白与沃勒变性及随后的神经再生过程中髓鞘胆固醇的挽救和再利用有关。目前的证据表明，髓鞘胆固醇与载脂蛋白E和A-I形成复合物，进而形成脂蛋白，这些脂蛋白通过髓鞘形成雪旺细胞上的低密度脂蛋白受体被摄取。然而，我们最近报道，神经再生或髓鞘胆固醇的再利用并不需要载脂蛋白E。我们现在研究了缺乏载脂蛋白E和A-I的突变小鼠的神经再生和胆固醇再利用情况。挤压伤后4周和12周对神经进行形态学检查发现，在缺乏这些载脂蛋白的情况下，神经以正常速度再生。对再生神经进行放射自显影表明，预先标记的髓鞘脂质在再生髓鞘中被再利用。胆固醇合成的限速酶3-羟基-3-甲基戊二酰辅酶A还原酶在再生神经中表达下调，这表明通过脂蛋白摄取胆固醇。预先标记的髓鞘胆固醇存在于从突变小鼠挤压神经中分离出的脂蛋白组分中。这些数据表明，神经内胆固醇再利用过程中存在相当大的冗余，并且除了载脂蛋白E和A-I之外的其他载脂蛋白可能参与髓鞘胆固醇的循环利用。
