Harry G J, Goodrum J F, Bouldin T W, Wagner-Recio M, Toews A D, Morell P
Department of Biochemistry, University of North Carolina, Chapel Hill 27599.
J Neurochem. 1989 Mar;52(3):938-45. doi: 10.1111/j.1471-4159.1989.tb02545.x.
Rats fed a diet containing 1.25% elemental tellurium initiated on postnatal day 20 undergo a transient neuropathy characterized by synchronous demyelination of peripheral nerves. In sciatic nerve, the extent of demyelination was maximal after 5 days of tellurium exposure; there was a loss of 25% of the myelin, as assayed by concentration of myelin-specific P0 protein. Tellurium-induced alterations in the metabolic capacity of Schwann cells were examined by measuring the synthesis of myelin lipids in vitro in isolated sciatic nerve segments. Exposure to tellurium resulted in an early marked decrease of approximately 50% in overall incorporation of [14C]acetate into lipids, with a preferential depression in synthesis of cerebrosides, cholesterol, and ethanolamine plasmalogens (components enriched in myelin). Most dramatically, within 1 day of initiation of tellurium exposure, there was a profound increase in [14C]acetate-derived radioactivity in squalene; 23% of incorporated label was in this intermediate of cholesterol biosynthesis, compared to less than 0.5% in controls. In association with the remyelinating phase seen after 5 days of tellurium exposure, synthesis of myelin components gradually returned to normal levels. After 30 days, metabolic and morphologic alterations were no longer apparent. We suggest that the sequence of metabolic events in sciatic nerve following tellurium treatment initially involves inhibition of the conversion of squalene to 2,3-epoxysqualene, and that this block in the cholesterol biosynthesis pathway results, either directly or indirectly, in the inhibition of the synthesis of myelin components and breakdown of myelin.
从出生后第20天开始喂食含1.25%元素碲饮食的大鼠会经历一种短暂性神经病变，其特征为外周神经同步性脱髓鞘。在坐骨神经中，碲暴露5天后脱髓鞘程度达到最大；通过髓鞘特异性P0蛋白浓度测定，髓鞘损失了25%。通过测量离体坐骨神经节段中髓鞘脂质的体外合成，研究了碲诱导的雪旺氏细胞代谢能力变化。碲暴露导致[14C]乙酸盐整体掺入脂质中早期显著下降约50%，其中脑苷脂、胆固醇和乙醇胺缩醛磷脂（髓鞘中富集的成分）的合成优先受到抑制。最显著的是，在碲暴露开始1天内，角鲨烯中[14C]乙酸盐衍生的放射性显著增加；掺入标记的23%存在于胆固醇生物合成的这个中间产物中，而对照组中这一比例不到0.5%。与碲暴露5天后出现的再髓鞘化阶段相关，髓鞘成分的合成逐渐恢复到正常水平。30天后，代谢和形态学改变不再明显。我们认为，碲处理后坐骨神经中的代谢事件序列最初涉及角鲨烯向2,3-环氧角鲨烯转化的抑制，并且胆固醇生物合成途径中的这一阻断直接或间接导致了髓鞘成分合成的抑制和髓鞘的分解。
