title: Formation of granular cytoplasmic aggregates in COS7 cells expressing mutant Cu/Zn superoxide dismutase associated with familial amyotrophic lateral sclerosis.
abstract: To investigate the molecular mechanisms of the 'gain of toxic function' of mutant Cu/Zn superoxide dismutase (SOD) associated with familial amyotrophic lateral sclerosis (FALS), mutant (Ala 4 --> Thr, Gly 85 --> Arg, Gly 93 --> Ala, and two base-pair deletion in the 126th codon), as well as wild-type (wt), Cu/Zn SODs were expressed in COS7 cells. The formation of granular cytoplasmic aggregates accompanied by collapse of the cytoplasm was observed in cells expressing mutant (mt) Cu/Zn SODs, but not in cells expressing wt Cu/Zn SOD. The aggregates contained ribosome-like particles and endoplasmic reticulum. These results suggest the possibility that mt Cu/Zn SODs promote the formation of aggregates which are toxic to cells.
authors.affiliation: Department of Neurology, Brain Research Institute, Niigata University, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Koide
authors.forename: S
authors.initials: S
authors.lastname: Igarashi
authors.forename: K
authors.initials: K
authors.lastname: Kikugawa
authors.forename: R
authors.initials: R
authors.lastname: Nakano
authors.forename: T
authors.initials: T
authors.lastname: Inuzuka
authors.forename: M
authors.initials: M
authors.lastname: Yamada
authors.forename: H
authors.initials: H
authors.lastname: Takahashi
authors.forename: S
authors.initials: S
authors.lastname: Tsuji
mesh_terms: D019943:Amino Acid Substitution; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000473:pathology*; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D003593:Cytoplasm / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D003594:Cytoplasmic Granules / Q000201:enzymology* / Q000473:pathology / Q000648:ultrastructure; D015870:Gene Expression; D008928:Mitochondria / Q000201:enzymology; D009154:Mutation; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics*; D013997:Time Factors; D014162:Transfection
chemical_list: D013482:Superoxide Dismutase