NDLI: Isolation of a diterpenoid substance with potent neuroprotective activity from fetal calf serum.

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Isolation of a diterpenoid substance with potent neuroprotective activity from fetal calf serum.

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Isolation of a diterpenoid substance with potent neuroprotective activity from fetal calf serum.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Yonaga, Masahiro Shimohama, Shun Osakada, Fumitaka Terauchi, Taro Kaneko, Shuji Sugimoto, Hachiro Nishizawa, Yukio Asai, Naoki Nishikawa, Hiroyuki Katsuki, Hiroshi Kume, Toshiaki Asakawa, Naoki Mano, Nariyasu Mori, Hiroki Taguchi, Ryota Akaike, Akinori Shirakawa, Hisashi
Description	Author Affiliation: Kume T ( Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.);
Abstract	Excess activation of glutamate receptors and production of free radicals including nitric oxide may result in severe and irreversible damage to the mammalian central nervous system (CNS), but endogenous defense systems that protect neurons from these insults are poorly understood. Here, we purified and isolated a neuroprotective substance, which has been named 'serofendic acid,' from a lipophilic fraction of FCS based on the ability to protect rat primary cortical neurons against nitric oxide cytotoxicity. Mass spectrometry and NMR spectroscopy revealed the chemical structure of serofendic acid (15-hydroxy-17-methylsulfinylatisan-19-oic acid) as a sulfur-containing atisane-type diterpenoid, which is unique among known endogenous substances. Synthetic serofendic acid exhibited potent protective actions on cortical neurons against cytotoxicity of a nitric oxide donor as well as of glutamate, although it did not show appreciable influences on glutamate receptor-mediated responses in these neurons. Electron spin resonance analysis demonstrated that serofendic acid had no direct scavenging activity on nitric oxide radicals but was capable of inhibiting the generation of hydroxyl radical, a presumed 'executor' radical in the nitric oxide-mediated neurotoxic cascade. These findings suggest that serofendic acid is a low-molecular-weight bioactive factor that promotes survival of CNS neurons, probably through the attenuation of free radical-mediated insults.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	5
Volume Number	99
Language	English
Publisher	National Academy of Sciences
Publisher Date	2002-03-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Diterpenes Pharmacology Neurons Drug Effects Neuroprotective Agents Animals Cells, Cultured Cerebral Cortex Cytology Isolation & Purification Molecular Structure Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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