Title of article :
Glial cell type-specific responses to menadione-induced oxidative stress
Author/Authors :
Scott B. Hollensworth، نويسنده , , Cheun-Chen Shen، نويسنده , , Julia E. Sim، نويسنده , , Douglas R. Spitz، نويسنده , , Glenn L. Wilson، نويسنده , , Susan P. LeDoux، نويسنده ,
Issue Information :
روزنامه با شماره پیاپی سال 2000
Pages :
14
From page :
1161
To page :
1174
Abstract :
Glial cell types in the central nervous system are continuously exposed to reactive oxygen species (ROS) due to their high oxygen metabolism and demonstrate differential susceptibility to certain pathological conditions believed to involve oxidative stress. The purpose of the current studies was to test the hypothesis that mtDNA damage could contribute to the differential susceptibility of glial cell types to apoptosis induced by oxidative stress. Primary cultures of rat astrocytes, oligodendrocytes, and microglia were utilized, and menadione was used to produce the oxidative stress. Apoptosis was detected and quantitated in menadione-treated oligodendrocytes and microglia (but not astrocytes) using either positive annexin-V staining or positive staining for 3′-OH groups in DNA. The apoptotic pathway that was activated involved the release of cytochrome c from the intermitochondrial space and activation of caspase 9. Caspase 8 was not activated after exposure to menadione in any of the cells. Using equimolar concentrations of menadione, more initial damage was observed in mtDNA from oligodendrocytes and microglia. Additionally, using concentrations of menadione that resulted in comparable initial mtDNA damage, more efficient repair was observed in astrocytes compared to either oligodendrocytes or microglia. The differential susceptibility of glial cell types to oxidative damage and apoptosis did not appear related to cellular antioxidant capacity, because under the current culture conditions astrocytes had lower total glutathione content and superoxide dismutase activity than oligodendrocytes and microglia. These results show that the differential susceptibility of glial cell types to menadione-induced oxidative stress and apoptosis appears to correlate with increased oxidative mtDNA damage and support the hypothesis that mtDNA damage could participate in the initiation of apoptosis through the enhanced release of cytochrome c and the activation of caspase 9.
Keywords :
Mn superoxide dismutase , oxidative stress , free radicals , DNA damage , DNA repair , reactive oxygen species , Apoptosis , Glia , mitochondria , glutathione
Journal title :
Free Radical Biology and Medicine
Serial Year :
2000
Journal title :
Free Radical Biology and Medicine
Record number :
518505
Link To Document :
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