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Research ArticleArticle

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 and Yee-Shin Lin
Molecular Pharmacology August 2006, 70 (2) 510-517; DOI: https://doi.org/10.1124/mol.106.024059
Chia-Ling Chen
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Chiou-Feng Lin
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Chi-Wu Chiang
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Ming-Shiou Jan
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Yee-Shin Lin
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Abstract

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.

  • Received March 3, 2006.
  • Accepted May 8, 2006.
  • The American Society for Pharmacology and Experimental Therapeutics
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Molecular Pharmacology: 70 (2)
Molecular Pharmacology
Vol. 70, Issue 2
1 Aug 2006
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Research ArticleArticle

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 and Yee-Shin Lin
Molecular Pharmacology August 1, 2006, 70 (2) 510-517; DOI: https://doi.org/10.1124/mol.106.024059

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Research ArticleArticle

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 and Yee-Shin Lin
Molecular Pharmacology August 1, 2006, 70 (2) 510-517; DOI: https://doi.org/10.1124/mol.106.024059
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