The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Long Term Lithium Treatment Suppresses p53 and Bax Expression but Increases Bcl-2 Expression
Open accessAbstract
This study was undertaken to investigate the molecular mechanisms underlying the neuroprotective actions of lithium against glutamate excitotoxicity with a focus on the role of proapoptotic and antiapoptotic genes. Long term, but not acute, treatment of cultured cerebellar granule cells with LiCl induces a concentration-dependent decrease in mRNA and protein levels of proapoptotic p53 and Bax; conversely, mRNA and protein levels of cytoprotective Bcl-2 are remarkably increased. The ratios of Bcl-2/Bax protein levels increase by approximately 5-fold after lithium treatment for 5-7 days. Exposure of cerebellar granule cells to glutamate induces a rapid increase in p53 and Bax mRNA and protein levels with no apparent effect on Bcl-2 expression. Pretreatment with LiCl for 7 days prevents glutamate-induced increase in p53 and Bax expression and maintains Bcl-2 in an elevated state. Glutamate exposure also triggers the release of cytochrome c from the mitochondria into the cytosol. Lithium pretreatment blocks glutamate-induced cytochrome c release and cleavage of lamin B1, a nuclear substrate for caspase-3. These results strongly suggest that lithium-induced Bcl-2 up-regulation and p53 and Bax down-regulation play a prominent role in neuroprotection against excitotoxicity. Our results further suggest that lithium, in addition to its use in the treatment of bipolar depressive illness, may have an expanded use in the intervention of neurodegeneration.
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Cites
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Cited by
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Enhancement of Hippocampal Neurogenesis by Lithium
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Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments
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Low glial numbers in the amygdala in major depressive disorder
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Metadata
- Authors
- Chen, R.-W., & Chuang, D.-M.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-03
- Volume
- 274
- Issue
- 10
- Pages
- 6039-6042
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2073264699
- Cited by
- 469
- References
- 27
- FWCI
- 11.42
- Type
- journal article
- Language
- en
- Open access
- hybrid
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- Chen, R.-W., & Chuang, D.-M. (1999). Long Term Lithium Treatment Suppresses p53 and Bax Expression but Increases Bcl-2 Expression. Journal of Biological Chemistry. https://doi.org/10.1074/jbc.274.10.6039
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