Role of Neu4L sialidase and its substrate ganglioside GD3 in neuronal apoptosis induced by catechol metabolites

Takafumi Hasegawa, Naoto Sugeno, Atsushi Takeda, Michiko Matsuzaki-Kobayashi, Akio Kikuchi, Katsutoshi Furukawa, Taeko Miyagi, Yasuto Itoyama

Research output: Contribution to journalArticlepeer-review

38 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)406-412
Number of pages7
JournalFEBS Letters
Volume581
Issue number3
DOIs
Publication statusPublished - 2007 Feb 6

Keywords

  • Apoptosis
  • Ganglioside GD3
  • Mitochondria
  • Neu4L
  • Neuronal death
  • Sialidase

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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