Studies on the local control by nerve growth factor of the outgrowth of neurites in PC12D cells.

在PC12D细胞中，神经突的生长不仅受到NGF的影响，还受到bFGF、abcAMP或staurosporine的影响。在NGF或bFGF处理的细胞中，可以观察到MAP激酶的同时激活和核易位。而staurosporine和abcAMP则没有或只有轻微的MAPK激活。由于PC12D细胞与引物细胞之间的相似性，MAPK的激活和核易位可能是转录依赖性分化步骤所必需的，但可能不是神经突伸长所必需的。加入蛋白质合成抑制剂环己亚胺后，PC12D细胞的神经突生长不会被阻断，环己亚胺中的蛋白质合成减少了97%。我们研究了NGF对PC12D细胞神经生长的局部控制。(1) NGF可诱导去核PC12D细胞的神经突生长和存活。(2)单个细胞（融合PC12D细胞）的巨突可独立响应NGF。(3)巨神经突在含NGF的培养基中维持时间较长。(4)神经生长因子对皱褶的快速形成似乎是基于细胞-基质黏附的增加，导致随后神经突的形成。这表明神经生长因子依赖性的神经突维持或延伸可能在神经突内部受到控制。任何ngf促进的变化，促进细胞基质粘附的局部增加，都可能导致神经突的延伸和起始。

The outgrowth of neurites was induced in PC12D cells that were treated not only with NGF but also with bFGF,abcAMP,or staurosporine. Simultaneous activation and nuclear translocation of MAP kinases were observed in cells treated with NGF or bFGF.But staurosporine and abcAMP induced no or slight activation of MAPK.Because of the similarity between PC12D cells and primed cells, the activation and nuclear translocation of MAPK might be required for transcriptiondependent differentiation step but might not be necessary for the elongation of neurites. The outgrowth of neurites from PC12D cells was not blocked by the addition of a protein-synthesis inhibitor, cycloheximide in which protein synthesis was reduced by 97%. We have examined to demonstrate local contral by NGF of the outgrowth of neuries from PC12D cells. (1) The neurite outgrowth and their survival can be induced by NGF in enucleated PC12D cells. (2) Individual giant neurites of a single cell (fused PC12D cells) can respond independently to the NGF.(3) The dissected giant neurites are maintained longer in medium containing NGF than not. (4) The rapid formation of ruffles in response to NGF which appears to be based on increased cell-substratum adhesion, lead to the subsequent formation of neurites. The observation indicates that the NGF-dependent maintenance or extension of neurites might be controlled within the neurites themselves. Any NGF-promoted changes that promote a local increase in cellsubstratum adhesion could be responsible for elongation and initiation of neurites.