Endogenous Factors Regulating Neuronal Death Induced by Radical Stress(Mitochondria and Neuroprotection)
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概要
- 論文の詳細を見る
Neurons in the central nervous system (CNS) are vulnerable to radical stress caused by reactive oxygen species, including nitric oxide (NO). Those radicals play crucial roles in glutamate neurotoxicity associated with ischemic brain injury and a wide range of neurodegenerative disorders. In our previous studies, we have shown evidence suggesting that glutamate neurotoxicity is regulated by certain endogenous substances such as neurotrophins, nicotinic acetylcholine, prostanoids and vitamins. Based on those findings, we have used the term 'neuroprotective factor' for endogenous substances possessing protective activity against glutamate neurotoxicity, and have further searched for a candidate with unique structure. We isolated a novel neuroprotective substance named 'serofendic acid' derived from fetal calf serum. The compound exhibited potent protective action against neurotoxicity induced by glutamate and by an NO donor without inhibiting glutamate receptors. Electron spin resonance analysis demonstrated that serofendic acid had no direct scavenging activity on NO, but was capable of inhibiting the generation of a hydroxyl radical, a presumed 'executor' radical in the nitric oxide-mediated neurotoxic cascade. The chemical structure was determined by mass spectrometry and nuclear magnetic resonance spectroscopy, and was confirmed by synthesis. The structure was unique among known endogenous substances because the compound was a sulfur-containing atisane type diterpenoid. The discovery of serofendic acid may provide a new scope for the investigation of low-molecular weight bioactive factors promoting the survival of CNS neurons.
- 公益社団法人日本薬学会の論文
- 2004-07-01
著者
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Katsuki Hiroshi
Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto
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Kume Toshiaki
京都大学 薬学研究科生体機能解析学
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Kume Toshiaki
京都大学 薬学研究科薬品作用解析学分野
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Kume Toshiaki
京都大学 薬学研究科薬品作用解析学
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Kume Toshiaki
同志社女子大学 医療薬学科薬理学
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Kume Toshiaki
Department Of Pharmaceutical Science Kyoto University Graduate School Of Pharmacology
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Akaike A
Department Of Pharmacology Graduate School Of Pharmaceutical Sciences Kyoto University
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Akaike Akinori
京都大学 薬学研究科生体機能解析学
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Akaike Akinori
京都薬科大学 病態生理
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Akaike Akinori
Department Of Pharmacology Graduate School Of Pharmaceutical Sciences Kyoto University
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Kume Toshiaki
Department Of Pharmacology Faculty Of Pharmaceutical Sciences Kyoto University
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Akaike Akinori
Department Of Pharmaceutical Science Kyoto University Graduate School Of Pharmacology
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Katsuki Hiroshi
Department Of Chemical Pharmacology Faculty Of Pharmaceutical Sciences The University Of Tokyo
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Akaike Akinori
Dep. Of Pharmacology Graduate School Of Pharmaceutical Sciences Kyoto Univ. Jpn
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Katsuki Hiroshi
Department Of Chemico-pharmacological Sciences Graduate School Of Pharmaceutical Sciences Kumamoto U
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Kume T
Department Of Pharmacology Graduate School Of Pharmaceutical Sciences Kyoto University
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Akaike Akinori
Department of Neuropharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
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