Cultured glial cells are resistant to the effects of motor neurone disease-associated SOD1 mutations.
Free radical damage has been implicated in the pathophysiology of motor neurone disease (MND); mutations have been identified in the gene encoding Cu/Zn superoxide dismutase (SOD1). There is evidence that glial cell dysfunction may contribute to motor neurone injury, but the exact role of glial cells in MND has yet to be established. The aim of this study was to determine whether expression of mutant SOD1 affects the response of glia to oxidative stress. Stable C6 glioma cells expressing mutant SOD1 and cortical astrocyte cultures from G93A-SOD1 transgenic mice were exposed to: xanthine/xanthine oxidase; hydrogen peroxide; A23187 and 3-morpholinosydonimine. Cell viability was measured using the 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Neither C6 glioma cells nor cortical astrocytes expressing mutant SOD1 were more susceptible to any of the free radical generating systems compared to control cells. These results suggest that astrocytes are resistant to the toxic effects of mutant SOD1 widely reported for neuronal cells.
Williams
R E
RE
Department of Neurology, The Medical School, University of Newcastle, Newcastle upon Tyne, UK.
Cookson
M R
MR
Fray
A E
AE
Manning
P M
PM
Menzies
F M
FM
Figlewicz
D A
DA
Shaw
P J
PJ
D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002490:Central Nervous System / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D005609:Free Radicals / Q000378:metabolism / Q000494:pharmacology; D005910:Glioma; D051379:Mice; D008822:Mice, Transgenic; D016472:Motor Neuron Disease / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D009046:Motor Neurons / Q000201:enzymology / Q000473:pathology; D009154:Mutation / Q000187:drug effects / Q000502:physiology*; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D013482:Superoxide Dismutase / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology
D005609:Free Radicals; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1