| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Research Abstract |
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
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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
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