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BCL-2 blocks glutamate toxicity in neural cell lines
L T Zhong1, D J Kane, D E Bredesen
1Department of Neurology, UCLA School of Medicine 90024-1769.
Abstract:
Glutamate has been shown, at high concentrations (5-10 mM), to lead to death in cells of the pheochromocytoma cell line PC12. We report that similar concentrations of glutamate also kill immortalized central neural cell lines, and that the expression of the proto-oncogene bcl-2 in these cell lines blocks glutamate neurotoxicity. Potassium chloride (25 mM) also protects a cerebellar neuronal cell line, but not PC12 cells, from glutamate toxicity.
Insights
High glutamate concentrations kill central neural cell lines. Expressing the bcl-2 gene protected these cells from glutamate neurotoxicity, suggesting a role for bcl-2 in neuronal survival.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- Glutamate is a key neurotransmitter.
- High concentrations of glutamate can cause excitotoxicity and neuronal death.
- The pheochromocytoma cell line PC12 is a common model for neuronal studies.
Purpose of the Study:
- To investigate the effect of high glutamate concentrations on immortalized central neural cell lines.
- To determine if the proto-oncogene bcl-2 can protect neural cells from glutamate neurotoxicity.
- To examine the protective effect of potassium chloride on glutamate toxicity in different neuronal cell lines.
Main Methods:
- Utilized immortalized central neural cell lines and the PC12 cell line.
- Exposed cells to high concentrations of glutamate (5-10 mM).
- Investigated the role of bcl-2 expression in cellular resistance to glutamate.
- Tested the neuroprotective effects of potassium chloride (25 mM).
Main Results:
- High glutamate concentrations induced cell death in immortalized central neural cell lines, similar to PC12 cells.
- The expression of the proto-oncogene bcl-2 significantly blocked glutamate-induced neurotoxicity.
- Potassium chloride (25 mM) protected a cerebellar neuronal cell line but not PC12 cells from glutamate toxicity.
Conclusions:
- Glutamate neurotoxicity affects various immortalized central neural cell lines.
- The proto-oncogene bcl-2 plays a protective role against glutamate excitotoxicity.
- Differential effects of potassium chloride suggest cell-type specific mechanisms in glutamate toxicity response.