Protective effect of epidermal growth factor on glutamate neurotoxicity in cultured cerebellar neurons.
The effects of epidermal growth factor (EGF) on glutamate-induced neuronal death were investigated in primary cultures of dissociated cerebellar neurons from fetal rats. Addition of an excess concentration of L-glutamate (5 mM) to the culture medium greatly decreased the number of surviving neurons 24 h later. When EGF was added to the culture medium 20 h prior to exposure to glutamate, glutamate-induced neuronal death was significantly reduced. The protective effects of EGF on glutamate neurotoxicity were concentration-dependent in the range of 0.01-10 ng/ml. When EGF was added 1 h prior to exposure to glutamate, it did not prevent glutamate-induced neuronal death, indicating that a longer exposure period is required for EGF to exert its protective effects. Furthermore, the protective effects of EGF on glutamate neurotoxicity disappeared in the presence of cycloheximide (0.1 microM), a protein synthesis inhibitor. These results suggest that EGF can protect brain neurons against glutamate toxicity through some protein synthesis.
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
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Abe
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Saito
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D003513:Cycloheximide / Q000494:pharmacology; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists; D005260:Female; D005971:Glutamates / Q000633:toxicity; D018698:Glutamic Acid; D009474:Neurons / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains
D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D018698:Glutamic Acid; D004815:Epidermal Growth Factor; D003513:Cycloheximide