N-methyl-D-aspartate receptor agonists decrease protooncogene bcl-2 mRNA expression in cultured rat cerebellar granule neurons.
The protooncogene bcl-2 was studied as a candidate gene for N-methyl-D-aspartate-(NMDA)-induced excitoprotection of cerebellar granule neurons. Exposure of these neurons to excitoprotective concentrations of NMDA and to excitotoxic concentrations of glutamate decreased bcl-2 mRNA levels. Preexposure to NMDA failed to modify the glutamate-evoked decrease in bcl-2 mRNA but increased neuronal survival from 20% to 100%. Neither the intracellular mechanisms underlying the cascade of excitoprotection induced by NMDA nor those underlying the cascade of glutamate toxicity of cerebellar granule neurons seem to specifically involve changes in bcl-2 mRNA levels. Glutamate did not induce nucleosomal DNA fragmentation but glutamate toxicity was inhibited by aurintricarboxylic acid. Glutamate toxicity of cerebellar granule neurons differs considerably from classical programmed cell death.
Montpied
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P
Section on Molecular Pharmacology, National Institute of Mental Health, Bethesda, Maryland.
Weller
M
M
Paul
S M
SM
D000199:Actins / Q000096:biosynthesis; D000818:Animals; D001312:Aurintricarboxylic Acid / Q000494:pharmacology; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005971:Glutamates / Q000494:pharmacology*; D018698:Glutamic Acid; D007700:Kinetics; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000096:biosynthesis; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2; D011519:Proto-Oncogenes / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D000199:Actins; D005971:Glutamates; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D001312:Aurintricarboxylic Acid; D016202:N-Methylaspartate; D011505:Protein-Tyrosine Kinases