Susceptibility of cerebellar granule neurons derived from Bcl-2-deficient and transgenic mice to cell death.
Overproduced Bcl-2 oncoprotein has been shown to suppress cell death induced by a variety of stimuli in many cell types, including neuronal cells. Because bcl-2 is expressed in the nervous system where massive cell death is observed during development, endogenous Bcl-2 is likely to be involved in regulating neuronal cell death. Here we examined the possible role of endogenous Bcl-2 in the regulation of neuronal cell survival in the central nervous system using primary cultured cerebellar granule neurons from bcl-2-deficient, wild-type and NSE-bcl-2-transgenic mice. Cerebellar granule neurons from bcl-2-deficient mice were more susceptible than those from normal littermates to death induced by reducing the K+ concentration of the medium from high (25 mM) to low (5 mM), and neurons from bcl-2-transgenic mice were least susceptible. Similar results were obtained when cell death was induced by serum withdrawal under high K+ conditions or by the presence of etoposide, A23187 or nimodipine. Consistently, bcl-2 deficiency reduced the number of cerebellar granule neurons per mouse. These results indicate that Bcl-2 impedes neuronal cell death induced by various stimuli in a dose-dependent manner, and that endogenous levels of Bcl-2 are able to regulate neuronal cell survival in the central nervous system.
Tanabe
H
H
Department of Molecular Genetics, Biomedical Research Center, Osaka University Medical School, Suita, Japan.
Eguchi
Y
Y
Kamada
S
S
Martinou
J C
JC
Tsujimoto
Y
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D000001:Calcimycin / Q000494:pharmacology; D002470:Cell Survival; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000502:physiology*; D003433:Crosses, Genetic; D016895:Culture Media, Serum-Free; D053938:DNA Fragmentation; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011188:Potassium / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D013997:Time Factors
D016895:Culture Media, Serum-Free; D019253:Proto-Oncogene Proteins c-bcl-2; D000001:Calcimycin; D005047:Etoposide; D011188:Potassium