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PMID:9153592

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Citation

Tanabe, H, Eguchi, Y, Kamada, S, Martinou, JC and Tsujimoto, Y (1997) Susceptibility of cerebellar granule neurons derived from Bcl-2-deficient and transgenic mice to cell death. Eur. J. Neurosci. 9:848-56

Abstract

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.

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Keywords

Animals; Apoptosis/drug effects; Calcimycin/pharmacology; Cell Survival; Cells, Cultured; Cerebellum/cytology; Cerebellum/physiology; Crosses, Genetic; Culture Media, Serum-Free; DNA Fragmentation; Etoposide/pharmacology; Humans; Mice; Mice, Inbred ICR; Mice, Knockout; Mice, Transgenic; Neurons/cytology; Neurons/drug effects; Neurons/physiology; Polymerase Chain Reaction; Potassium/pharmacology; Proto-Oncogene Proteins c-bcl-2/deficiency; Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/physiology; Time Factors

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


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