Abstract
We examined the effects of oxidative stress on rat cultured mesencephalic neurons and glial cells. Glial cells were more resistant to 6- hydroxydopamine (6-OHDA) and H2O2 toxicity than neurons. In glial cells, incubation with 6-OHDA and H2O2 induced a significant increase in the expression of γ-glutamylcysteine synthetase (the rate-limiting enzyme in glutathione synthesis) mRNA, which correlated well with increased TPA- response element (TRE)-binding activity. Furthermore, a subsequent elevation in cellular total glutathione content was also observed. In neurons, both agents decreased TRE-binding activity, and these cells failed to up-regulate the glutathione synthesis. We also examined the mechanisms of the neuroprotective effects of glial cells using a gila conditioned medium. Neurons maintained in gila conditioned medium up-regulated the level of TRE- binding activity, γ-glutamylcysteine synthetase mRNA expression, and total glutathione content in response to 6-OHDA or H2O2, and became more resistant to both agents than cells maintained in a normal medium. Neurons maintained in normal medium failed to up-regulate the glutathione synthesis. Our results suggest that transcriptional up-regulation of glutathione synthesis in glial cell appears to mediate brain glial cell resistance against oxidative stress, and that glial cells protect neurons via transcriptional up-regulation of the antioxidant system.
| Original language | English |
|---|---|
| Pages (from-to) | 2334-2344 |
| Number of pages | 11 |
| Journal | Journal of Neurochemistry |
| Volume | 72 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - 1999 |
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Keywords
- Conditioned medium
- Cultured glias
- Cultured neurons
- Glutathione
- Oxidative stress
- Transcriptional regulation
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience
Cite this
Glial cells protect neurons against oxidative stress via transcriptional up-regulation of the glutathione synthesis. / Iwata-Ichikawa, Emi; Kondo, Yoichi; Miyazaki, Ikuko; Asanuma, Masato; Ogawa, Norio.
In: Journal of Neurochemistry, Vol. 72, No. 6, 1999, p. 2334-2344.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Glial cells protect neurons against oxidative stress via transcriptional up-regulation of the glutathione synthesis
AU - Iwata-Ichikawa, Emi
AU - Kondo, Yoichi
AU - Miyazaki, Ikuko
AU - Asanuma, Masato
AU - Ogawa, Norio
PY - 1999
Y1 - 1999
N2 - We examined the effects of oxidative stress on rat cultured mesencephalic neurons and glial cells. Glial cells were more resistant to 6- hydroxydopamine (6-OHDA) and H2O2 toxicity than neurons. In glial cells, incubation with 6-OHDA and H2O2 induced a significant increase in the expression of γ-glutamylcysteine synthetase (the rate-limiting enzyme in glutathione synthesis) mRNA, which correlated well with increased TPA- response element (TRE)-binding activity. Furthermore, a subsequent elevation in cellular total glutathione content was also observed. In neurons, both agents decreased TRE-binding activity, and these cells failed to up-regulate the glutathione synthesis. We also examined the mechanisms of the neuroprotective effects of glial cells using a gila conditioned medium. Neurons maintained in gila conditioned medium up-regulated the level of TRE- binding activity, γ-glutamylcysteine synthetase mRNA expression, and total glutathione content in response to 6-OHDA or H2O2, and became more resistant to both agents than cells maintained in a normal medium. Neurons maintained in normal medium failed to up-regulate the glutathione synthesis. Our results suggest that transcriptional up-regulation of glutathione synthesis in glial cell appears to mediate brain glial cell resistance against oxidative stress, and that glial cells protect neurons via transcriptional up-regulation of the antioxidant system.
AB - We examined the effects of oxidative stress on rat cultured mesencephalic neurons and glial cells. Glial cells were more resistant to 6- hydroxydopamine (6-OHDA) and H2O2 toxicity than neurons. In glial cells, incubation with 6-OHDA and H2O2 induced a significant increase in the expression of γ-glutamylcysteine synthetase (the rate-limiting enzyme in glutathione synthesis) mRNA, which correlated well with increased TPA- response element (TRE)-binding activity. Furthermore, a subsequent elevation in cellular total glutathione content was also observed. In neurons, both agents decreased TRE-binding activity, and these cells failed to up-regulate the glutathione synthesis. We also examined the mechanisms of the neuroprotective effects of glial cells using a gila conditioned medium. Neurons maintained in gila conditioned medium up-regulated the level of TRE- binding activity, γ-glutamylcysteine synthetase mRNA expression, and total glutathione content in response to 6-OHDA or H2O2, and became more resistant to both agents than cells maintained in a normal medium. Neurons maintained in normal medium failed to up-regulate the glutathione synthesis. Our results suggest that transcriptional up-regulation of glutathione synthesis in glial cell appears to mediate brain glial cell resistance against oxidative stress, and that glial cells protect neurons via transcriptional up-regulation of the antioxidant system.
KW - Conditioned medium
KW - Cultured glias
KW - Cultured neurons
KW - Glutathione
KW - Oxidative stress
KW - Transcriptional regulation
UR - http://www.scopus.com/inward/record.url?scp=0032973861&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0032973861&partnerID=8YFLogxK
U2 - 10.1046/j.1471-4159.1999.0722334.x
DO - 10.1046/j.1471-4159.1999.0722334.x
M3 - Article
C2 - 10349842
AN - SCOPUS:0032973861
VL - 72
SP - 2334
EP - 2344
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 6
ER -