Evidence that Protein Kinase C Activities Involved in Regulating Neurite Growth Are Localized to Distal Neurites
Evidence that Protein Kinase C Activities Involved in Regulating Neurite Growth Are Localized to Distal Neurites
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证据表明参与调节神经突生长的蛋白激酶 C 活性局限于远端神经突
DOI：
10.1046/j.1471-4159.1994.63030868.x
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发表时间：
1994
影响因子：
4.7
通讯作者：
D. Senger
中科院分区：
文献类型：
--
作者：
R. Campenot;Dwight D. Draker;D. Senger
摘要：之前，我们观察到，用phorbol 12‐肉豆蔻酸酯13‐乙酸酯（PMA）长期处理大鼠交感神经元远端神经纤维，可使神经突伸长率降低50%。在本报告中，我们表明，通过测定PKC特异性八肽底物的Ca2+依赖性磷酸化，可以测量远端神经突提取物中的PKC活性。我们发现，1µM PMA局部应用于远端神经突24小时，导致以这种方式测量的Ca2+依赖性PKC活性几乎完全下调。我们确定PMA对神经突伸长的抑制是由神经突的局部机制介导的，因为PMA局部应用于含有细胞体和近端神经突的中心室并没有抑制远端神经突的伸长率。然后，我们研究了最近可用的PKC抑制剂calphostin C和chelerythrine的作用，发现与PMA一样，这些抑制剂局部应用于远端神经突时可以抑制远端神经突的生长，而应用于细胞体和近端神经突时则没有效果。然而，calphostin C对神经突生长的抑制发生在远低于其蛋白激酶抑制的IC50值的浓度下，即使在PMA预处理的神经元中，calphostin C和车车草碱也抑制了远端神经突的生长。因此，这些药物似乎并不都通过相同的机制抑制神经突的生长。尽管在交感神经元中参与神经突伸长的PKC活性尚未被精确定义，但本研究的数据表明，生长锥上的蛋白激酶在调节轴突生长中起着复杂而重要的作用。
Abstract: Previously, we observed that long‐term treatment of distal nerve fibers of rat sympathetic neurons in compartmented cultures with phorbol 12‐myristate 13‐acetate (PMA) caused a reduction in the rate of neurite elongation by >50%. In the present report we show that protein kinase C (PKC) activity could be measured in extracts of distal neurites by an assay of the Ca2+‐dependent phosphorylation of a PKC‐specific octapeptide substrate. We found that local application of 1 µM PMA for 24 h to distal neurites caused nearly complete down‐regulation of Ca2+‐dependent PKC activity measured in this manner. We determined that the inhibition of neurite elongation by PMA was mediated by local mechanisms in the neurites because local application of PMA to center compartments containing cell bodies and proximal neurites did not inhibit the rate of elongation of distal neurites. We then investigated the effects of the recently available PKC inhibitors, calphostin C and chelerythrine, finding that, like PMA, these inhibited the growth of distal neurites when applied locally to them, and had no effect when applied to cell bodies and proximal neurites. However, the inhibition of neurite growth by calphostin C occurred at a concentration far below its IC50 value for protein kinase inhibition, and both calphostin C and chelerythrine inhibited distal neurite growth even in neurons pretreated with PMA. Thus, it appears that these agents do not all inhibit neurite growth through the same mechanisms. Although the PKC activities involved in neurite elongation in sympathetic neurons have not been precisely defined, these data presented in this study indicate that protein kinases localized to growth cones play a complex and important role in regulating axonal growth.
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DOI：
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发表时间：
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DOI：
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DOI：
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发表时间：
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期刊：
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