TY - JOUR T1 - Lithium Inhibits Ceramide- and Etoposide-Induced Protein Phosphatase 2A Methylation, Bcl-2 Dephosphorylation, Caspase-2 Activation, and Apoptosis JF - Molecular Pharmacology JO - Mol Pharmacol SP - 510 LP - 517 DO - 10.1124/mol.106.024059 VL - 70 IS - 2 AU - Chia-Ling Chen AU - Chiou-Feng Lin AU - Chi-Wu Chiang AU - Ming-Shiou Jan AU - Yee-Shin Lin Y1 - 2006/08/01 UR - http://molpharm.aspetjournals.org/content/70/2/510.abstract N2 - 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. ER -