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.
Abe
K
K
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Saito
H
H
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