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Calcium-dependent prevention of neuronal apoptosis by lithium ion: essential role of phosphoinositide 3-kinase and phospholipase Cgamma.
- Source :
-
Molecular pharmacology [Mol Pharmacol] 2003 Aug; Vol. 64 (2), pp. 228-34. - Publication Year :
- 2003
-
Abstract
- We examined the possibility that the neuroprotective effects of Li+ would depend upon the patterns of neuronal death, apoptosis versus necrosis, and whether Ca2+ as well as phosphoinositide 3-kinase (PI3-K) would mediate the neuroprotective effect of Li+. Cortical neurons treated with Li+ showed marked increase in [Ca2+]i within 2 min. Addition of BAPTA-acetoxymethyl ester, a selective Ca2+ chelator, abrogated the antiapoptotic effect of Li+. PI3-K was activated rapidly within 1 min after exposure to Li+, which mediated Ca2+-dependent neuroprotective effects of Li+. Activated PI3-K seemed to increase [Ca2+]i via the phospholipase Cgamma (PLCgamma) pathway. Antiapoptosis action of Li+ was prevented in the presence of U-73122, a selective phospholipase C inhibitor, and was not observed in PLCgamma1-null fibroblasts. In contrast to antiapoptosis action, administration of Li+ did not prevent neuronal cell necrosis by excitotoxicity or free radicals. Li+ selectively prevents apoptosis by increasing [Ca2+]i through activation of PI3-K and PLCgamma pathways.
Details
- Language :
- English
- ISSN :
- 0026-895X
- Volume :
- 64
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 12869627
- Full Text :
- https://doi.org/10.1124/mol.64.2.228