The neural cell adhesion molecule (N-CAM) inhibits proliferation in primary cultures of rat astrocytes.
The neural cell adhesion molecule (N-CAM) inhibits proliferation in primary cultures of rat astrocytes.
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DOI：
10.1073/pnas.92.2.542
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发表时间：
1995-01
影响因子：
11.1
通讯作者：
O. Sporns;G. Edelman;K. L. Crossin
中科院分区：
文献类型：
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作者：
O. Sporns;G. Edelman;K. L. Crossin
细胞增殖是神经发育过程中关键的初级过程，在神经组织对损伤的再生反应中也发挥着重要作用。据报道，神经胶质细胞增殖至少部分是由神经元信号控制的，可能涉及细胞表面分子。我们在此报告，在大鼠前脑星形胶质细胞的原代培养物中添加纯化的大鼠神经细胞粘附分子（N-CAM）可抑制其增殖。这种抑制作用可以在化学成分确定的无血清培养基或补充有生长因子的培养基中产生。 N-CAM 或其 Fab' 片段的多克隆抗体引起了类似的抑制作用。 N-CAM 的抑制作用的大小取决于细胞密度：在低细胞密度时抑制作用最大，并随着细胞接近汇合而逐渐减弱。具有与 N-CAM 推定的同源结合区域相同的序列的合成肽模拟了纯化的 N-CAM 的效果，而具有相同长度和氨基酸组成但具有随机序列的肽则不然。在原代星形胶质细胞培养物中添加 N-CAM 反义寡核苷酸 48 小时，导致 N-CAM 表达水平降低。通过这种处理降低星形胶质细胞上的 N-CAM 水平后，添加到培养基中的 N-CAM 的抗增殖作用显着降低。综合结果表明，N-CAM 亲同性结合可能参与神经胶质细胞增殖的控制。
Cell proliferation is a key primary process during neural development and also plays an important role in the regenerative response of neural tissue to injury. It has been reported that glial cell proliferation is, at least in part, controlled by a neuronal signal, possibly involving cell surface molecules. We report here that the addition of purified rat neural cell adhesion molecule (N-CAM) to primary cultures of rat forebrain astrocytes inhibits their proliferation. This inhibitory effect can be elicited in cultures grown in chemically defined serum-free medium or in medium that had been supplemented with growth factors. Polyclonal antibodies to N-CAM or their Fab' fragments elicited a similar inhibitory effect. The magnitude of the inhibitory effect of N-CAM was dependent on cell density: it was maximal at low cell densities and weakened progressively as cells approached confluency. Synthetic peptides with sequences identical to a putative homophilic binding region of N-CAM mimicked the effect of purified N-CAM, while peptides of the same length and amino acid composition but with a randomized sequence did not. The addition of N-CAM antisense oligonucleotides to primary astrocyte cultures for 48 h resulted in reduced levels of N-CAM expression. After N-CAM levels on astrocytes were diminished by this treatment, the antiproliferative effect of N-CAM added to the medium was significantly reduced. The combined results suggest that N-CAM homophilic binding may be involved in the control of glial cell proliferation.