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大鼠中结构多肽的轴突慢速运输、链脲佐菌素诱导糖尿病的早期变化及胰岛素治疗的效果

Slow axonal transport of structural polypeptides in rat, early changes in streptozocin diabetes, and effect of insulin treatment.

作者信息

Larsen J R, Sidenius P

机构信息

Diabetes Research Laboratory, Second University Clinic of Internal Medicine, Aarhus, Denmark.

出版信息

J Neurochem. 1989 Feb;52(2):390-401. doi: 10.1111/j.1471-4159.1989.tb09134.x.

DOI:10.1111/j.1471-4159.1989.tb09134.x
PMID:2463334
Abstract

The synthesis and transport of slowly transported polypeptides in sciatic nerves of rats was investigated by [35S]methionine pulse labeling and gel electrophoresis in control, diabetic, and insulin-treated diabetic rats. To detect very early changes diabetes was induced by streptozocin only 5 days prior to the labeling of the dorsal root ganglion cells. Fourteen days were allowed for axonal transport. In this experimental system, the neurofilament triplet is transported at an apparent velocity of 1.1 +/- 0.1 mm/day (mean +/- SD). The actin-related complex, including actin and two polypeptides of 87 kilodaltons and 37 kilodaltons, was transported at a velocity of 2.6 +/- 0.2 mm/day. For alpha- and beta-tubulin we found an apparent transport velocity of 2.2 +/- 0.1 mm/day, placing it between actin and the neurofilament triplet. The diabetic rats had a selective 32% decrease in the amount of the heaviest neurofilament subunit: 0.47 +/- 0.19% of trichloroacetic acid-insoluble radioactivity versus 0.69 +/- 0.17% in controls; 2p less than 0.05. This decrease was associated with a proximal accumulation of the two lighter neurofilament subunits. Insulin treatment of a diabetic group failed to normalize the changes of axonal transport and additional changes suggesting a hypoglycemic injury was observed.

摘要

通过[35S]甲硫氨酸脉冲标记和凝胶电泳,对正常、糖尿病及胰岛素治疗的糖尿病大鼠坐骨神经中慢运输多肽的合成和运输进行了研究。为检测极早期变化,仅在标记背根神经节细胞前5天用链脲佐菌素诱导糖尿病。给予14天时间进行轴突运输。在该实验系统中,神经丝三联体以1.1±0.1毫米/天(平均值±标准差)的表观速度运输。包括肌动蛋白以及87千道尔顿和37千道尔顿两种多肽的肌动蛋白相关复合物,以2.6±0.2毫米/天的速度运输。对于α-和β-微管蛋白,我们发现其表观运输速度为2.2±0.1毫米/天,介于肌动蛋白和神经丝三联体之间。糖尿病大鼠最重的神经丝亚基数量选择性减少32%:三氯乙酸不溶性放射性的0.47±0.19%,而对照组为0.69±0.17%;P<0.05。这种减少与两个较轻神经丝亚基在近端的积累有关。对糖尿病组进行胰岛素治疗未能使轴突运输的变化恢复正常,并且观察到了提示低血糖损伤的其他变化。

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