Role of Neu4L sialidase and its substrate ganglioside GD3 in neuronal apoptosis induced by catechol metabolites |
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Authors: | Hasegawa Takafumi Sugeno Naoto Takeda Atsushi Matsuzaki-Kobayashi Michiko Kikuchi Akio Furukawa Katsutoshi Miyagi Taeko Itoyama Yasuto |
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Institution: | Department of Neurology, Tohoku University School of Medicine, Sendai, Miyagi 980-8574, Japan. |
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Abstract: | 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. |
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Keywords: | Sialidase Neu4L Ganglioside GD3 Mitochondria Apoptosis Neuronal death |
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