Signal transduction alterations in peripheral nerves from streptozotocin-induced diabetic rats.
Signal transduction alterations in peripheral nerves from streptozotocin-induced diabetic rats.
复制标题
链脲佐菌素诱导的糖尿病大鼠周围神经信号转导的改变。
DOI：
10.1002/jnr.490410411
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Berti-Mattera,LN
中科院分区：
文献类型：
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作者：
Goraya,TY;Wilkins,P;Douglas,JG;Zhou,J;Berti-Mattera,LN
我们以前已经确定了存在的毒蕈碱受体和几个G蛋白的表达在匀浆和髓鞘馏分从RA坐骨神经。在本研究中，我们调查了周围神经中几种信号转导途径的变化是否可能导致某些生化异常（例如，磷酸肌醇代谢）。用[3 H]-肌肌醇预标记的5周糖尿病大鼠坐骨神经显示出肌醇单磷酸和二磷酸的基础释放显著增加，而氨甲酰胆碱刺激的释放显著较小。糖尿病动物坐骨神经匀浆中基础和毛喉素刺激的腺苷酸环化酶活性显著降低。然而，我们无法检测到任何显着差异的cAMP水平在完整的神经或神经节段中，在存在或不存在毛喉素的情况下孵育。ADP-核糖基化实验表明，在实验性糖尿病大鼠的坐骨神经中，霍乱和百日咳毒素催化的ADP-核糖基化显著增加。对G蛋白a-亚基水平的测量显示，Gq/11α、Gsα和Gi-3α的表达增加了30%至50%。这些结果表明，在实验性糖尿病的过程中，周围神经表现出磷酸肌醇和cAMP的异常产生，以及G蛋白的异常表达和/或功能。这种改变的后果之一是减少释放磷酸肌醇触发毒蕈碱激动剂在糖尿病坐骨神经。© 1995 Wiley利斯公司
We have previously determined the presence of muscarinic receptors and the expression of several G proteins in homogenates and myelin fractions from ra sciatic nerves. In the present study we investigates whether changes in several signal transduction path ways in peripheral nerves might be responsible for some of the biochemical abnormalities (e.g., phosphoinositide metabolism) present in sciatic nerves from streptozotocin‐induced diabetic rats. Sciatic nerves from 5 week diabetic rats that were prelabelled with [3H]‐myo‐inositol displayed a significant increase in the basal release of inositol mono‐and bis‐phosphate, while carbamylcholine‐stimulated release was significantly smaller. Basal‐ and forskolinstimulated adenylyl cyclase activity was significantly decreased in sciatic nerve homogenates from diabetic animals. However, we were unable to detect any significant differences in the levels of cAMP in intact nerves or in nerve segments that were incubated in the presence or absence of forskolin. ADP‐ribosylation experiments showed that in sciatic nerves from experimentally diabetic rats there was a significant increase in the ADP‐ribosylation catalyzed by cholera and pertussis toxins. Measurements of the levels of a‐subunits of G proteins revealed that the expression of Gq/11α, Gsα, and Gi‐3α was increased by 30 to 50%. These results indicate that during the course of experimental diabetes, peripheral nerves exhibit an abnormal production of inositol phosphates and cAMP, together with an abnormal expression and/or function of G proteins. One of the consequences of such alterations is the diminished release of inositol phosphates triggered by muscarinic agonists in diabetic sciatic nerves. © 1995 Wiley‐Liss, Inc.