寿命蛋白質のｃＤＮＡクローニングおよび中枢神経における栄養因子作用機序の研究

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  • 道川 誠
    国立長寿医療研究センター痴呆疾患研究部

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  • cDNA Cloning of Ju-myo Protein (JP) and Elucidation of the Molecular Mechanisms by Which It Exerts Neurotrophic Effects on Neurons.
  • ジュミョウ タンパクシツ ノ cDNA クローニング オヨビ チュウスウ シンケイ ニ オケル エイヨウ インシ サヨウ キジョ ノ ケンキュウ

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The adult life span in inbred strains of Drosophila melanogaster (Dm) has been found to be controlled by a few major genes (Hereditas 111: 207, 1989; Hereditas 117: 251, 1992). A 77kDa protein, which we named ju-myo (life-span) protein (JP) and is supposed to be the product of the gene on autosomal locus JmA on adult Dm was shown to have life-span prolonging effect when it was supplied in food. However, the knowledge of its structure and molecular mechanisms by which JP exerts its effects on cells is still unclear. Here we show that JP can exert neurotrophic activities on postmitotic fetal rat neurons isolated from cerebral cortical and dopaminergic neurons isolated from the midbrain: it enhanced survival of MAP2-positive cells and tyrosine hydroxylase immunoreactive neurons by approximately 2-fold over the control group. JP did not increase the density of astrocytes nor expression of glial fibrillary acidic protein (GFAP) in the mesencephalic neuron cultures. Aminoacid analysis of JP protein showed that JP is identical to the larval serum protein 2, of which sequence and structure were determined in 1997. Our work provides basis for defining the physiological role of JP at the molecular level and for exploring its potential utility as an alternative approach to study mechanisms of aging.

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