Elucidation of function of astrocytes appearedin aded brain and its inducing factor

9.研究结果概要星形胶质细胞被认为在中枢神经系统功能的发育和维持中起重要作用，它与神经元和其它胶质细胞协同作用。星形胶质细胞膜上的多糖在细胞间通讯中起着重要作用。植物凝集素是研究该问题的有效工具，因为植物凝集素与某些细胞表面受体的结合可以引发通常由这些受体的内源性配体激活的细胞反应。在本研究中，我们研究了曼陀罗凝集素（DSA）对星形胶质细胞的影响，并阐明了以下分子事件。将DSA添加到来自新生大鼠小脑的扁平、多角形、未成熟的星形胶质细胞的培养物中，诱导细胞形态改变为星状形式，类似于体内观察到的星形胶质细胞，伴随着星形胶质细胞特异性增加。 ...更多信息 特异性中间丝（GFAP）和增殖抑制。结果表明，DSA与星形胶质细胞结合并触发分化。为了阐明星形胶质细胞分化过程中的分子事件，我们研究了各种信号转导抑制剂对星形胶质细胞的影响。只有酪氨酸磷酸酶抑制剂，orthovanadate和氧化苯胂，表现出抑制作用。伴随着这些现象，我们发现在38-KD蛋白的酪氨酸磷酸化的程度下降。结果表明，DSA诱导星形胶质细胞分化通过酪氨酸去磷酸化。我们开发的系统将有助于阐明星形胶质细胞分化过程中的分子事件。由于DSA和半乳糖凝集素-1（Gal-1）的碳水化合物结合特异性相似，我们研究了Gal-1是否诱导星形胶质细胞分化。向未成熟星形胶质细胞中加入Gal-1诱导细胞分化。细胞变得具有长突起，并且它们的生长受到抑制。此外，它们还增加了GFAP的表达。乳糖特异性地抑制Gal-1的分化。这些结果表明，脑内还原型Gal-1的功能是诱导星形胶质细胞分化。少

Tokyo Metropolitan Institute of Gerontology, Department of Glycobiology, Researcher 0 9.SUMMARY OF RESEARCH RESULTS Astrocytes are considered to be important in the development and maintenance of functions of the central nervous system, acting in cooperation with neurons and other glial cells. The glycans on astrocyte membrane are supposed to play important roles in cell-cell communication. Plant lectins are useful tools to probe it, because the binding lectins to certain cell surface receptors can elicitthe cellular responses that normally activated by endogenous ligands forthose receptors. In the present study, we investigated the effect Datura stramonium agglutinin (DSA) on astrocytes and elucidated the following molecular events. Addition of DSA to aculture of flat, polygonal, immature astrocytes derived from the neonatal rat cerebellum induced morphological change of the cells to the stellate form, similar to astrocytes observed in vivo, concomitant with increase of astrocyte spec … More ific intermediate filament (GFAP) and inhibition of proliferation. The results indicatethat DSA binds to astrocytes and triggers differentiation. To elucidate of molecular events during astrocyte differentiation, we examined the effects of various signal transduction inhibitors on stellation. Only the tyrosine phosphatase inhibitors, orthovanadate and phenylarsine oxide, showed an inhibitory effect. Concomitantly with these phenomena, we found a decrease in the extent of tyrosine-phosphorylation of a38-KD protein. The results suggest that DSA induces astrocyte differentiation through tyrosine dephosphorylation. Our developed system will be useful to elucidate the molecular events during astrocyte differentiation. Since the carbohydrate-binding specificity of DSA and Galectin-1 (Gal-1) is similar, we examined whether Gal-1 induces astrocyte differentiation. Addition of Gal-1 to aculture of immature astrocytes induced differentiation of the cells. The cells became bearing long processes and their growth was inhibited. In addition, they increased the expression of GFAP. Differentiation by Gal-1 was inhibited with lactose specifically. These results indicatethat afunction of reduced form Gal-1 in brain is induction of astrocyte differentiation. Less