title: Caspase activation during apoptotic cell death induced by expanded polyglutamine in N2a cells.
abstract: Huntington disease (HD) is an autosomal dominant neurodegenerative disorder. To investigate the mechanism of neurodegeneration induced by mutant huntingtin, we developed a stable neuro2a cell line expressing truncated N-terminal huntingtin (tNhtt) with EGFP using the ecdysone-inducible system. The formation of aggregates and the cell death induced by expression of tNhtt with expanded polyglutamine was repeat length- and dose-dependent. Caspases were activated, and the death substrates of caspases, lamin B and ICAD (an inhibitor of caspase-activated DNase), were cleaved in this cell death process. The cleavage of lamin B was inhibited by caspase inhibitors. These findings suggest that the cell death induced by tNhtt with expanded polyglutamine is mediated by caspases.
authors.affiliation: Laboratory for CAG repeat diseases, RIKEN Brain Science Institute, Saitama, Japan.
authors.forename: G H
authors.initials: GH
authors.lastname: Wang
authors.forename: K
authors.initials: K
authors.lastname: Mitsui
authors.forename: S
authors.initials: S
authors.lastname: Kotliarova
authors.forename: A
authors.initials: A
authors.lastname: Yamashita
authors.forename: Y
authors.initials: Y
authors.lastname: Nagao
authors.forename: S
authors.initials: S
authors.lastname: Tokuhiro
authors.forename: T
authors.initials: T
authors.lastname: Iwatsubo
authors.forename: I
authors.initials: I
authors.lastname: Kanazawa
authors.forename: N
authors.initials: N
authors.lastname: Nukina
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000187:drug effects*; D004789:Enzyme Activation; D005799:Genes, Dominant; D006816:Huntington Disease / Q000235:genetics / Q000503:physiopathology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D009447:Neuroblastoma; D010455:Peptides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D010455:Peptides; C097188:polyglutamine; D020169:Caspases