Eckenstein F P, Shipley G D, Nishi R
Department of Cell Biology and Anatomy, Oregon Health Sciences University, Portland 97201.
J Neurosci. 1991 Feb;11(2):412-9. doi: 10.1523/JNEUROSCI.11-02-00412.1991.
Acidic and basic fibroblast growth factors (aFGF and bFGF) are known to stimulate mitogenesis in a variety of non-neuronal cell types. Recent work has also established that FGFs can act as neurotrophic factors that promote the survival and regeneration in vitro of a variety of neurons. The present study investigates the distribution of aFGF and bFGF in vivo by using a mitogenic bioassay on AKR-2B cells coupled with Western-blot analysis to estimate the levels of aFGF and bFGF in different areas of the rat nervous system. Acidic FGF and bFGF from extracts of nervous tissue were found to differ considerably in their relative dependencies upon heparin to potentiate their mitogenic activities: the effect of aFGF was strongly dependent upon heparin, whereas the effect of bFGF was only slightly potentiated by heparin. Heparin was also found to stimulate differentially the mitogenic activity of extracts prepared from different areas of the nervous system, indicating that spinal cord, cortex, pituitary, and optic nerve contained different ratios of aFGF to bFGF, whereas sciatic nerve contained extremely high levels of only aFGF. These results were confirmed in Western-blot experiments, using antibodies specific for either aFGF or bFGF. Transection of nerves had opposing effects in sciatic and optic nerves: aFGF rapidly declined in the sciatic nerve distal to the cut, whereas bFGF increased slightly in the distal portion of the cut optic nerve. This differential effect of injury on FGF levels in central versus peripheral nerves may reflect the differential regenerative potential of these two types of nerves.
酸性和碱性成纤维细胞生长因子(aFGF和bFGF)已知可刺激多种非神经元细胞类型的有丝分裂。最近的研究还证实,FGF可作为神经营养因子,促进多种神经元在体外的存活和再生。本研究通过对AKR-2B细胞进行有丝分裂生物测定并结合蛋白质印迹分析,以估计大鼠神经系统不同区域中aFGF和bFGF的水平,从而研究aFGF和bFGF在体内的分布情况。结果发现,神经组织提取物中的酸性FGF和bFGF在增强其有丝分裂活性对肝素的相对依赖性方面存在很大差异:aFGF的作用强烈依赖于肝素,而bFGF的作用仅被肝素轻微增强。还发现肝素对神经系统不同区域制备的提取物的有丝分裂活性有不同的刺激作用,这表明脊髓、皮质、垂体和视神经中aFGF与bFGF的比例不同,而坐骨神经中仅aFGF含量极高。使用针对aFGF或bFGF的特异性抗体进行的蛋白质印迹实验证实了这些结果。神经横断对坐骨神经和视神经有相反的影响:切断部位远端的坐骨神经中aFGF迅速下降,而切断的视神经远端部分的bFGF略有增加。损伤对中枢神经和外周神经中FGF水平的这种差异作用可能反映了这两种神经不同的再生潜力。