Role of Neu4L sialidase and its substrate ganglioside GD3 in neuronal apoptosis induced by catechol metabolites.
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.
Hasegawa
Takafumi
T
Department of Neurology, Tohoku University School of Medicine, Sendai, Miyagi 980-8574, Japan.
Sugeno
Naoto
N
Takeda
Atsushi
A
Matsuzaki-Kobayashi
Michiko
M
Kikuchi
Akio
A
Furukawa
Katsutoshi
K
Miyagi
Taeko
T
Itoyama
Yasuto
Y
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
D002396:Catechols; D018076:DNA, Complementary; D005732:Gangliosides; C026226:ganglioside, GD3; D014442:Monophenol Monooxygenase; C491428:NEU4 protein, human; D009439:Neuraminidase