Lithium inhibits ceramide- and etoposide-induced protein phosphatase 2A methylation, Bcl-2 dephosphorylation, caspase-2 activation, and apoptosis

Chia-Ling Chen, Chiou Feng Lin, Chi-Wu Chiang, Ming-Shiou Jan, Yee-Shin Lin

研究成果: 雜誌貢獻文章同行評審

59 引文 斯高帕斯(Scopus)

摘要

Lithium confers cell protection against stress and toxic stimuli. Although lithium inhibits a number of enzymes, the antiapoptotic mechanisms of lithium remain unresolved. Here, we report a novel role of lithium on the blockage of ceramide- and etoposide-induced apoptosis via inhibition of protein phosphatase 2A (PP2A) activity. Overexpression of PP2A resulted in caspase-2 activation, mitochondrial damage, and cell apoptosis that were inhibited by okadaic acid (OA) and lithium. Lithium and OA abrogated ceramide- and etoposide-induced Bcl-2 dephosphorylation at serine 70. Furthermore, ceramide- and etoposide-induced PP2A activation involved methylation of PP2A C subunit, which lithium suppressed. Lithium caused dissociation of PP2A B subunit from the PP2A core enzyme, whereas ceramide caused recruitment of the B subunit. Taken together, lithium exhibited an antiapoptotic effect by inhibiting Bcl-2 dephosphorylation and caspase-2 activation, which involved, at least in part, a mechanism of down-regulating PP2A methylation and PP2A activity.
原文英語
頁(從 - 到)510-517
頁數8
期刊Molecular Pharmacology
70
發行號2
DOIs
出版狀態已發佈 - 2006

ASJC Scopus subject areas

  • 藥理

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