Asano T, Aoyagi M, Hirakawa K, Ikawa Y
Department of Neurosurgery, Tokyo Medical and Dental University, School of Medicine, Japan.
J Neurooncol. 1994;18(1):1-7. doi: 10.1007/BF01324597.
In addition to its powerful vasoconstrictive activity, endothelin-1 (ET-1) has been recognized to stimulate DNA synthesis in some cell lines. In this study, we confirmed the existence of ET-1 receptor in YKG-1 human glioma cells, and investigated its effect on DNA synthesis in YKG-1 for 6 consecutive days, comparing it with that of epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and insulin-like growth factor-I (IGF-I). Scatchard analysis of the binding data revealed the presence of a single class of high-affinity binding molecule. The apparent dissociation constant (Kd) was 5.2 x 10(-9) M and the maximal binding capacity (B max) was 4.7 x 10(4) sites/cell. The percentage of non-cycling cells was initially more than 85%, and decreased to 55.40%, 24.22%, 11.50%, and 7.51% on days 1, 2, 4, and 6, respectively, after ET-1 stimulation. Although ET-1 reduces the fraction of non-cycling cells more slowly than other growth factors such as EGF, PDGF and IGF-I, it reaches the same level as the others by day 6. These results indicate that YKG-1 human glioma cells have ET-1 receptors and that ET-1 initiates a peculiar slow induction of DNA synthesis in these cells, suggesting that secondary factors might exist to accelerate the DNA synthesis in response to ET-1.
除了具有强大的血管收缩活性外,内皮素-1(ET-1)还被认为能刺激某些细胞系中的DNA合成。在本研究中,我们证实了YKG-1人胶质瘤细胞中存在ET-1受体,并连续6天研究了其对YKG-1细胞DNA合成的影响,同时与表皮生长因子(EGF)、血小板衍生生长因子(PDGF)和胰岛素样生长因子-I(IGF-I)进行比较。对结合数据进行Scatchard分析显示存在一类单一的高亲和力结合分子。表观解离常数(Kd)为5.2×10^(-9) M,最大结合容量(B max)为4.7×10^4个位点/细胞。ET-1刺激后,非循环细胞的百分比最初超过85%,在第1、2、4和6天分别降至55.40%、24.22%、11.50%和7.51%。尽管ET-1比其他生长因子如EGF、PDGF和IGF-I更缓慢地降低非循环细胞的比例,但到第6天时它达到了与其他因子相同的水平。这些结果表明YKG-1人胶质瘤细胞具有ET-1受体,并且ET-1在这些细胞中引发了一种特殊的缓慢的DNA合成诱导,这表明可能存在二级因子来加速对ET-1的DNA合成反应。