Role of Neu4L sialidase and its substrate ganglioside GD3 in neuronal apoptosis induced by catechol metabolites
Role of Neu4L sialidase and its substrate ganglioside GD3 in neuronal apoptosis induced by catechol metabolites
复制标题
DOI：
10.1016/j.febslet.2006.12.046
复制
发表时间：
2007-02-06
期刊：
影响因子：
3.5
通讯作者：
Itoyama, Yasuto
中科院分区：
文献类型：
--
作者：
Hasegawa, Takafumi;Sugeno, Naoto;Itoyama, Yasuto
哺乳动物唾液酸酶是糖复合物降解的关键酶。Neu 4L唾液酸酶定位于线粒体并在脑中特异性表达。为了阐明Neu 4L在神经系统中的病理生理作用，我们研究了Neu 4L在酪氨酸酶产生的儿茶酚代谢产物存在下的凋亡性神经变性中的可能参与。我们证明：（i）Neu 4L的表达水平在凋亡前显著降低;（ii）凋亡表型的特征在于细胞色素c释放到胞质溶胶中，伴随着神经节苷脂GD 3向线粒体的运输;和（iii）葡糖神经酰胺合酶抑制剂部分恢复了细胞活力。Neu 4L及其底物GD 3可能是神经细胞线粒体凋亡途径中的关键分子。(c)2007年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Mammalian sialidases are key enzymes in the degradation of glycoconjugates. Neu4L sialidase is localized to mitochondria and specifically expressed in brain. To elucidate the pathophysiological roles of Neu4L in the nervous system, we investigated the possible involvement of Neu4L in the apoptotic neurodegeneration under the existence of catechol metabolites generated by tyrosinase. We demonstrated that: (i) the expression level of Neu4L was dramatically decreased prior to apoptosis; (ii) the apoptotic phenotype was characterized by cytochrome c release into cytosol concomitant with the trafficking of ganglioside GD3 to mitochondria; and (iii) the inhibitor of glucosylceramide synthase partially recovered cell viability. Neu4L and its substrate GD3 may act as key molecules in the mitochondrial apoptotic pathway in neuronal cells. (c) 2007 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.