カワジリ　スミヒロ   KAWAJIRI Sumihiro   河尻　澄宏    所属   医学部 医学科（附属東洋医学研究所）    職種   准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	P150glued-associated disorders are caused by activation of intrinsic apoptotic pathway.
掲載誌名	正式名：PloS one 略　 称：PLoS One ISSNコード：19326203/19326203
掲載区分	国外
巻・号・頁	9(4),pp.e94645
著者・共著者	Ishikawa Kei-Ichi, Saiki Shinji, Furuya Norihiko, Yamada Daisuke, Imamichi Yoko, Li Yuanzhe, Kawajiri Sumihiro, Sasaki Hironori, Koike Masato, Tsuboi Yoshio, Hattori Nobutaka
発行年月	2014
概要	Mutations in p150glued cause hereditary motor neuropathy with vocal cord paralysis (HMN7B) and Perry syndrome (PS). Here we show that both overexpression of p150glued mutants and knockdown of endogenous p150glued induce apoptosis. Overexpression of a p150glued plasmid containing either a HMN7B or PS mutation resulted in cytoplasmic p150glued-positive aggregates and was associated with cell death. Cells containing mutant p150glued aggregates underwent apoptosis that was characterized by an increase in cleaved caspase-3- or Annexin V-positive cells and was attenuated by both zVAD-fmk (a pan-caspase inhibitor) application and caspase-3 siRNA knockdown. In addition, overexpression of mutant p150glued decreased mitochondrial membrane potentials and increased levels of translocase of the mitochondrial outer membrane (Tom20) protein, indicating accumulation of damaged mitochondria. Importantly, siRNA knockdown of endogenous p150glued independently induced apoptosis via caspase-8 activation and was not associated with mitochondrial morphological changes. Simultaneous knockdown of endogenous p150glued and overexpression of mutant p150glued had additive apoptosis induction effects. These findings suggest that both p150glued gain-of-toxic-function and loss-of-physiological-function can cause apoptosis and may underlie the pathogenesis of p150glued-associated disorders.
DOI	10.1371/journal.pone.0094645
PMID	24722468