title: Serofendic acid prevents acute glutamate neurotoxicity in cultured cortical neurons.
abstract: We have previously reported that a novel neuroprotective substance named serofendic acid was purified and isolated from ether extract of fetal calf serum. In the present study, we investigated the effect of serofendic acid on acute neurotoxicity induced by L-glutamate (Glu) using primary cultures of rat cortical neurons. Exposure of cortical cultures to Glu for 1 h caused a marked decrease in cell viability, as determined by trypan blue exclusion. This acute Glu neurotoxicity was prevented by N-methyl-D-aspartate (NMDA) receptor antagonists, extracellular Ca(2+) removal, nitric oxide (NO) synthase inhibitor and NO scavenger. Serofendic acid prevented acute Glu neurotoxicity in a concentration-dependent manner. Acute neurotoxicity was induced by ionomycin, a Ca(2+) ionophore, and S-nitroso-L-cysteine, an NO donor. Serofendic acid also prevented both ionomycin- and S-nitroso-L-cysteine-induced neurotoxicity. Moreover, the protective effect of serofendic acid on acute Glu neurotoxicity was not affected by cycloheximide, a protein synthesis inhibitor, and actinomycin D, an RNA synthesis inhibitor. These results indicate that serofendic acid protects cultured cortical neurons from acute Glu neurotoxicity by reducing the cytotoxic action of NO and de novo protein synthesis is not required for this neuroprotection.
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Yoshida-shimoadachi-cho, Sakyo-ku, 606-8501, Kyoto, Japan.
authors.forename: Ryota
authors.initials: R
authors.lastname: Taguchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nishikawa
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Kume
authors.forename: Taro
authors.initials: T
authors.lastname: Terauchi
authors.forename: Shuji
authors.initials: S
authors.lastname: Kaneko
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katsuki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Yonaga
authors.forename: Hachiro
authors.initials: H
authors.lastname: Sugimoto
authors.forename: Akinori
authors.initials: A
authors.lastname: Akaike
mesh_terms: D000818:Animals; D002118:Calcium / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D003545:Cysteine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000378:metabolism; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology / Q000627:therapeutic use*; D016291:Dizocilpine Maleate / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005312:Fetal Blood / Q000737:chemistry; D005333:Fetus / Q000033:anatomy & histology; D015759:Ionomycin / Q000009:adverse effects / Q000037:antagonists & inhibitors; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000473:pathology*; D020258:Neurotoxicity Syndromes / Q000517:prevention & control*; D009569:Nitric Oxide / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D011810:Quinoxalines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D026403:S-Nitrosothiols / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000378:metabolism; D012970:Sodium Glutamate / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D004224:Diterpenes; D004338:Drug Combinations; D011810:Quinoxalines; D026403:S-Nitrosothiols; C452642:serofendic acid; D009569:Nitric Oxide; D015759:Ionomycin; C061603:6,7-dichloroquinoxaline-2,3-dione; D016291:Dizocilpine Maleate; C056639:2-amino-5-phosphopentanoic acid; C021315:S-nitrosocysteine; D014633:Valine; D003545:Cysteine; D002118:Calcium; D012970:Sodium Glutamate