Koide T, Igarashi S, Kikugawa K, Nakano R, Inuzuka T, Yamada M, Takahashi H, Tsuji S
Department of Neurology, Brain Research Institute, Niigata University, Japan.
Neurosci Lett. 1998 Nov 20;257(1):29-32. doi: 10.1016/s0304-3940(98)00800-3.
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.
为了研究与家族性肌萎缩侧索硬化症（FALS）相关的突变型铜锌超氧化物歧化酶（SOD）“毒性功能获得”的分子机制，将突变型（丙氨酸4→苏氨酸、甘氨酸85→精氨酸、甘氨酸93→丙氨酸以及第126密码子处两个碱基对缺失）和野生型（wt）铜锌SOD在COS7细胞中表达。在表达突变型（mt）铜锌SOD的细胞中观察到伴有细胞质塌陷的颗粒状细胞质聚集体的形成，而在表达wt铜锌SOD的细胞中未观察到。聚集体包含核糖体样颗粒和内质网。这些结果提示mt铜锌SOD促进对细胞有毒性的聚集体形成的可能性。
