J Korean Neurol Assoc.  2002 Sep;20(5):525-529.

Neuroprotective Effect of Estrogen on Motor Neuron Cells Expressing Wild Type or Mutant Cu/Zn Superoxide Dismutase

Affiliations
  • 1Department of Neurology, College of Medicine, Seoul National University, Korea. kwoo@plaza.snu.ac.kr
  • 2Department of Neurology, Seoul Municipal Boramae Hospital, Korea.

Abstract

BACKGROUND: Recently, the mechanism involved in nitric oxide (NO)-mediated motor neuron death is under extensive investigation. The role of Cu/Zn superoxide dismutase (SOD) mutation, which is found in about 2% of all ALS patients, has been implicated in selective motor neuron death and it is said to play an important role in NO-mediated motor neuron death. Estrogen is reported to have neuroprotective effect in various neurological diseases. However, neuroprotective effect on estradiol on spinal motor neuron exposed to NO has rarely been studied.
METHODS
Motor neuron-neuroblastoma hybrid cell expressing wild-type or mutant (G93A or A4V) SOD gene was treated with 200 micro M Snitrosoglutathione. After 24 hours, cell viability was measured by MTT assay. To see the neuroprotective effect of estradiol, pretreatment with 5 nM or 50 nM 17 beta-estradiols was done 24 hours before S-nitrosoglutathione treatment.
RESULTS
S-nitrosoglutathione showed significant neurotoxic effect in all three cell lines. Percentage of cell death was significantly different in each cell line. Both 5 nM and 50 nM estradiols showed neuroprotective effect in G93A cell line. In wild-type cell line, 50 nM estradiol showed neuroprotective effect, but 5 nM estradiol did not. In A4V cell line, estradiol did not showed neuroprotective effect.
CONCLUSIONS
This study showed that NO-mediated motor neuron death could be influenced by presence or absence of mutation and type of mutation in SOD gene. Neuroprotective effect of estradiol is also influenced by SOD gene mutation. This study implies that estrogen might be beneficial to some ALS patients.

Keyword

Amyotrophic lateral sclerosis (ALS); Cell viability; Neuroprotection; Cu/Zn superoxide dismutase (SOD); Nitric Oxide (NO); Estrogen

MeSH Terms

Cell Death
Cell Line
Cell Survival
Estradiol
Estrogens*
Humans
Hybrid Cells
Motor Neurons*
Neuroprotective Agents*
Nitric Oxide
S-Nitrosoglutathione
Superoxide Dismutase*
Superoxides*
Estradiol
Estrogens
Neuroprotective Agents
Nitric Oxide
S-Nitrosoglutathione
Superoxide Dismutase
Superoxides
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