title: Polyglutamine expansion disturbs the endoplasmic reticulum formation, leading to caspase-7 activation through Bax.
abstract: The endoplasmic reticulum (ER) plays a pivotal role in cellular functions such as the ER stress response. However, the effect of the ER membrane on caspase activation remains unclear. This study reveals that polyglutamine oligomers augmented at ER induce insertion of Bax into the ER membrane, thereby activating caspase-7. In line with the role of ER in cell death induced by polyglutamine expansion, the ER membrane was found to be disrupted and dilated in the brain of a murine model of Huntington's disease. We can conclude that polyglutamine expansion may drive caspase-7 activation by disrupting the ER membrane.
authors.affiliation: Department of Neurobiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Ueda
authors.affiliation: Department of Neurobiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Shimo
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Neurobiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Itoh
authors.affiliation: Department of Neurobiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Yoshika
authors.initials: Y
authors.lastname: Hayakawa-Yano
authors.affiliation: Department of Neurobiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Miao-xing
authors.initials: MX
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Miki
authors.initials: M
authors.lastname: Hayakawa
authors.affiliation: Department of Neurobiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Ryoko
authors.initials: R
authors.lastname: Hasebe-Matsubara
authors.affiliation: Department of Neurobiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Ohta
authors.affiliation: Department of Neurobiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Ohta
authors.affiliation: Department of Neurobiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Mizuno
authors.affiliation: Department of Neurobiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hida
authors.affiliation: Department of Neurobiology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Munekazu
authors.initials: M
authors.lastname: Matsumoto
authors.affiliation: Department of Anatomy, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Huayue
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Neurobiology, Gifu University Graduate School of Medicine, Gifu, Japan. Electronic address: tnakagaw@gifu-u.ac.jp.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Nakagawa
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000378:metabolism / Q000473:pathology; D053179:Caspase 7 / Q000378:metabolism*; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000473:pathology; D004789:Enzyme Activation; D057809:HEK293 Cells; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007425:Intracellular Membranes / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010455:Peptides / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism*
chemical_list: C494827:Bax protein, mouse; C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010455:Peptides; D051028:bcl-2-Associated X Protein; C097188:polyglutamine; C505524:Casp7 protein, mouse; D053179:Caspase 7
keywords: Apoptosis; Bcl-2 family; Caspase; Endoplasmic reticulum; Neurodegeneration; Polyglutamine expansion disorder