NO-induced apoptosis and ER stress in microglia.
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- KAWAHARA Kohichi
- Department of Molecular Cell Function, Graduate School of Pharmaceutical Sciences, Kumamoto University
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- MORI Masataka
- Department of Molecular Genetics, Graduate School of Medical Sciences, Kumamoto University
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- NAKAYAMA Hitoshi
- Department of Molecular Cell Function, Graduate School of Pharmaceutical Sciences, Kumamoto University
Bibliographic Information
- Other Title
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- ミクログリアにおけるNO誘導性アポトーシスと小胞体ストレス
- ミクログリア ニ オケル NO ユウドウセイ アポトーシス ト ショウホウタイ ストレス
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Description
Nitric Oxide (NO) produced by activated microglia is an important contributor to neuronal damage. NO toxicity is generally thought to be mediated by the DNA damage-p53 pathway or mitochondrial dysfunction. We investigated the mechanism of NO toxicity by using microglial MG5 cells established from p53-deficient mouse. When MG5 cells were exposed to LPS plus IFN-γ, mRNA and protein for inducible NO synthase (iNOS) were markedly induced and apoptosis occurred. Under these conditions, we found that mRNA and protein for CHOP/GADD153, a C/EBP family transcription factor that is involved in ER stress-induced apoptosis, were induced. These results suggest that NO-induced apoptosis in MG5 cells occurs through the ER stress pathway involving CHOP, but is independent of p53. Overactivation-induced apoptosis may be an essential self-regulatory mechanism for microglia in order to limit bystander killing of vulnerable neurons. On the other hand, recent reports suggest that there may exist two subtypes of microglia at least in the CNS. We found activated rat type-1 microglia induced expression of iNOS and exhibited neurotoxic to rat hippocampal neurons. By contrast, activated type-2 microglia hardly exhibited neurotoxicity in this co-culture system. These results suggest that the two subtype(s) of microglia may regulate differently the inflammatory response in the CNS.<br>
Journal
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- Folia Pharmacologica Japonica
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Folia Pharmacologica Japonica 124 (6), 399-406, 2004
The Japanese Pharmacological Society
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Details 詳細情報について
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- CRID
- 1390282679249830528
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- NII Article ID
- 10025739431
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- NII Book ID
- AN00198335
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- ISSN
- 13478397
- 00155691
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- NDL BIB ID
- 7167149
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- PubMed
- 15572844
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- Text Lang
- ja
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- Data Source
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- JaLC
- NDL Search
- Crossref
- PubMed
- CiNii Articles
- OpenAIRE
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- Abstract License Flag
- Disallowed