title: Role of Neu4L sialidase and its substrate ganglioside GD3 in neuronal apoptosis induced by catechol metabolites.
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.
authors.affiliation: Department of Neurology, Tohoku University School of Medicine, Sendai, Miyagi 980-8574, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Naoto
authors.initials: N
authors.lastname: Sugeno
authors.forename: Atsushi
authors.initials: A
authors.lastname: Takeda
authors.forename: Michiko
authors.initials: M
authors.lastname: Matsuzaki-Kobayashi
authors.forename: Akio
authors.initials: A
authors.lastname: Kikuchi
authors.forename: Katsutoshi
authors.initials: K
authors.lastname: Furukawa
authors.forename: Taeko
authors.initials: T
authors.lastname: Miyagi
authors.forename: Yasuto
authors.initials: Y
authors.lastname: Itoyama
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001483:Base Sequence; D001693:Biological Transport, Active / Q000187:drug effects; D002396:Catechols / Q000378:metabolism / Q000494:pharmacology; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D014442:Monophenol Monooxygenase / Q000378:metabolism; D009439:Neuraminidase / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D010084:Oxidation-Reduction; D013379:Substrate Specificity
chemical_list: D002396:Catechols; D018076:DNA, Complementary; D005732:Gangliosides; C026226:ganglioside, GD3; D014442:Monophenol Monooxygenase; C491428:NEU4 protein, human; D009439:Neuraminidase