Calcium-influx increases SOD1 aggregates via nitric oxide incultured motor neurons

다국어 초록 (Multilingual Abstract)

Familial amyotrophic lateral sclerosis (fALS) is caused by mutations in Cu/Zn-superoxide dismutase (SOD1), and SOD1 aggregation and calcium toxicity are in-volved in neuronal death. However, the effect of altered calcium homeostasis on the SOD1 aggregation is unknown. To investigate whether calcium triggers mu-tant SOD1 aggregation in vitro, human mutant SOD1 (G93A) was transfected into motor neuronal cell line cium ionophore A23187 or agents that induce intra-celular calcium release like cyclic ADP ribose, ryano-dine or thapsigargin. A23187 was found to increase mutant SOD1 aggregation and neuronal nitric oxide synthase (nNOS) expression. Moreover, the NOS in-hibitor (L-NAME) and a NO-dependent cyclic GMP cas-cade inhibitor (ODQ) reduced SOD1 aggregation, whereas an exogenous NO donor (GSNO) increased by NOS or cGMP cascade inhibitor. Our data demon-strate that calcium-influx increases SOD1 aggregation by upregulating NO in cultured motor neuronal cells.

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