Calcium-dependent prevention of neuronal apoptosis by lithium ion: Essential role of phosphoinositide 3-kinase and phospholipase Cγ

Hyo Jung Kang, Jai Sung Noh, Yun Soo Bae, Byoung Joo Gwag

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

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 Cγ (PLCγ) pathway. Antiapoptosis action of Li+ was prevented in the presence of U-73122, a selective phospholipase C inhibitor, and was not observed in PLCγ1-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 PLCγ pathways.

Original languageEnglish
Pages (from-to)228-234
Number of pages7
JournalMolecular Pharmacology
Volume64
Issue number2
DOIs
StatePublished - 1 Aug 2003

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