Role of nitric oxide in survival and death of neurons.
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- AKAIKE Akinori
- Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University
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- KATSUKI Hiroshi
- Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University
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- KUME Toshiaki
- Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University
Bibliographic Information
- Other Title
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- NOの病態生理 創薬への展開 神経細胞死・生存におけるNOの役割
- 神経細胞死・生存におけるNOの役割
- シンケイ サイボウシ セイゾン ニ オケル NO ノ ヤクワリ
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Abstract
The prominent pathological feature of the brain in Parkinson's disease is selective degeneration of dopaminergic neurons in the substantia nigra of the midbrain. Glutamate and nitric oxide (NO) are the major effectors of the radical stress that may induce selective loss of dopaminergic neurons. It has been postulated that neurotoxicity induced by glutamate and NO in dopaminergic neurons is regulated by certain endogenous factors. We have reported that estradiol protects dopaminergic neurons against NO-mediated glutamate neurotoxicity by reducing intracellular reactive oxygen species (ROS) levels. We further searched for a candidate for neuroprotective substances with unique structure. From the ether extract of fetal calf serum (FCS), we isolated a novel substance possessing protective activity against neurotoxicity induced by glutamate NO. The compound was a sulfur-containing diterpenoid and showed hydroxyl radical scavenging activity. We further analyzed the change of resistance to excitotoxicity in midbrain dopaminergic neurons in co-culture with the striatum by using a slice culture technique. The results suggested that the generation of NO is involved in NMDA cytotoxicity on dopaminergic neurons and that increased activity of SOD in co-culture renders dopaminergic neurons resistant to NMDA cytotoxicity by preventing peroxynitrite formation. Those findings suggest that regulation of intracellular ROS levels plays a critical role in protecting neurons against NO-mediated radical stress in neurodegenerative disorders.<br>
Journal
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- Folia Pharmacologica Japonica
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Folia Pharmacologica Japonica 119 (1), 15-20, 2002
The Japanese Pharmacological Society
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Details 詳細情報について
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- CRID
- 1390282679247093248
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- NII Article ID
- 10008181629
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- NII Book ID
- AN00198335
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- COI
- 1:STN:280:DC%2BD387islGksg%3D%3D
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- ISSN
- 13478397
- 00155691
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- NDL BIB ID
- 6026757
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- PubMed
- 11862752
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- Text Lang
- ja
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- Data Source
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- Abstract License Flag
- Disallowed