Protective effect of serofendic acid on glutamate-induced neurotoxicity in rat cultured motor neurons.
We have previously reported that a sulfur-containing neuroprotective substance named serofendic acid was purified and isolated from lipophilic extract of fetal calf serum (FCS). In the present study, we investigated the effect of serofendic acid on glutamate neurotoxicity using embryonic rat spinal cord culture. When cultures were exposed to glutamate (20 microM) with a glutamate transporter inhibitor L-trans-pyrrolidine-2,4-decarboxylate (PDC; 40 microM) for 24 h, motor neurons were injured through both N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methylisoxazole/kainate receptors. This glutamate neurotoxicity was attenuated by nitric oxide (NO) synthase inhibitors. Serofendic acid (0.1-5 microM) prevented glutamate neurotoxicity in a concentration-dependent manner. S-Nitrosocysteine (SNOC; 10 microM), an NO donor, induced motor neuronal death. Serofendic acid (5 microM) also prevented SNOC-induced neurotoxicity. These results indicate that serofendic acid protects cultured motor neurons from glutamate neurotoxicity by reducing the cytotoxic action of NO.
Kume
Toshiaki
T
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-cho, Kyoto 606-8501, Japan.
Kawai
Yuko
Y
Yoshida
Kohei
K
Nakamizo
Tomoki
T
Kanki
Rie
R
Sawada
Hideyuki
H
Katsuki
Hiroshi
H
Shimohama
Shun
S
Sugimoto
Hachiro
H
Akaike
Akinori
A
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D003545:Cysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D003998:Dicarboxylic Acids / Q000494:pharmacology; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004622:Embryo, Mammalian; D018698:Glutamic Acid / Q000633:toxicity*; D009046:Motor Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D026403:S-Nitrosothiols / Q000494:pharmacology; D013116:Spinal Cord / Q000166:cytology; D013997:Time Factors
D003998:Dicarboxylic Acids; D004224:Diterpenes; D018696:Neuroprotective Agents; D014179:Neurotransmitter Uptake Inhibitors; D020030:Nitric Oxide Donors; D011759:Pyrrolidines; D026403:S-Nitrosothiols; C452642:serofendic acid; D018698:Glutamic Acid; C021315:S-nitrosocysteine; C083486:pyrrolidine-2,4-dicarboxylic acid; D003545:Cysteine