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Glial Cells Protect Neurons Against Oxidative Stress via Transcriptional Up‐Regulation of the Glutathione Synthesis
Author(s) -
IwataIchikawa Emi,
Kondo Yoichi,
Miyazaki Ikuko,
Asanuma Masato,
Ogawa Norio
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0722334.x
Subject(s) - glutathione , oxidative stress , neuroprotection , neuroglia , microbiology and biotechnology , biology , neuron , glutathione synthetase , biochemistry , enzyme , central nervous system , endocrinology , pharmacology , neuroscience
We examined the effects of oxidative stress on ratcultured mesencephalic neurons and glial cells. Glial cells were moreresistant to 6‐hydroxydopamine (6‐OHDA) and H 2 O 2 toxicity than neurons. In glial cells, incubation with 6‐OHDA andH 2 O 2 induced a significant increase in the expression ofγ‐glutamylcysteine synthetase (the rate‐limiting enzyme in glutathionesynthesis) mRNA, which correlated well with increased TPA‐response element(TRE)‐binding activity. Furthermore, a subsequent elevation in cellular totalglutathione content was also observed. In neurons, both agents decreasedTRE‐binding activity, and these cells failed to up‐regulate the glutathionesynthesis. We also examined the mechanisms of the neuroprotective effects ofglial cells using a glia conditioned medium. Neurons maintained in gliaconditioned medium up‐regulated the level of TRE‐binding activity,γ‐glutamylcysteine synthetase mRNA expression, and total glutathionecontent in response to 6‐OHDA or H 2 O 2 , 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.