- J Korean Neurol Assoc. 2003;21(5):521-526.
- "The Effect of Calcium Modulators on Motoneuron Cells Which Express Mutated Cu / Zn Superoxide Dismutase"
- Sung Hun Kim
- "Department of Neurology, College of Medicine, Kangwon National University* Department of Neurology, College of Medicine, Seoul National University"
- "변이된 Cu/Zn superoxide dismutase를 발현하는 운동신경세포주에 칼슘조절제가 미치는 영향"
- 김성훈 , 김현정 김만호 이광우
- 강원대학교 의과대학 신경과학교실, 서울대학교 의과대학 신경과학교실
- Abstract
- "Background: Intracellular calcium accumulation and dys-regulation is known as one of the mechanism in motor neuronal
degeneration with mutations in Cu/Zn superoxide dismutase (SOD-1). Methods: To investigate the calcium modulators
and mutated SOD-1 induced neuronal death, we tested motoneuron-neuroblastoma hybrid (VSC 4.1) cells constitutively
expressing human SOD-1 gene with mutations (A4V, G93A) or wild type. Calcium mobilizer through cell
membrane (calcium ionophore; A23187) or endogenous calcium releaser (ryanodine, thapsigargin, cyclic ADP-ribose)
was treated and cell viabilities were determined by using a 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyl tetrazolium
bromide (MTT) assay. Apoptotic cell death was monitored by caspase enzyme assay and the Hoescht staining to check
the evidence of nuclear fragmentation. R e s u l t s: Among agents, calcium ionophore and tharpsigargin reduced the level of
survival in cells expressing mutant SOD-1. In mutant cells, caspase 3 activity was elevated and showed nuclear fragmentation.
This phenomenon was blocked by caspase inhibitor. C o n c l u s I o n s: Our data suggest that motor neuron degeneration
in familial amyotrophic lateral sclerosis with SOD-1 mutation may be mediated by calcium dys-regulation, particularly
by exogenous calcium influx and this process induces caspase 3 activity which results in motor neuron death.Key Words : Amyotrophic lateral sclerosis, Superoxide dismutase, Calcium, Cell death, Apoptosis, Caspase"
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