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.
journal_name
Proc Natl Acad Sci U S Aauthors
Kume T,Asai N,Nishikawa H,Mano N,Terauchi T,Taguchi R,Shirakawa H,Osakada F,Mori H,Asakawa N,Yonaga M,Nishizawa Y,Sugimoto H,Shimohama S,Katsuki H,Kaneko S,Akaike Adoi
10.1073/pnas.052693999keywords:
subject
Has Abstractpub_date
2002-03-05 00:00:00pages
3288-93issue
5eissn
0027-8424issn
1091-6490pii
052693999journal_volume
99pub_type
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