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• W2159590941 abstract "Glycogen synthase kinase-3β (GSK-3β) plays an important role in the regulation of apoptosis. To investigate its involvement in acquired cadmium (Cd) resistance, Cd-resistant cells (RH460) were established from H460 lung carcinoma cells. Cd resistance led to interruption of apoptosis and autophagy, as determined by an apoptotic sub-G1 population, procaspase-3 clevage, and LC3-II induction. Cd-induced autophagy preceded apoptosis as determined by 3-methyladenine or zVAD and time-course experiments after Cd treatment. Despite β-catenin accumulation, phospho(p)-Ser/Tyr GSK-3α/β increased in the nucleus until 12h after treatment and then p-Ser partly translocated to the cytoplasm. The GSK-3 inhibitor lithium augmented Cd-induced p-Ser GSK-3α/β, which accumulated in the nucleus and cytoplasm, and increased autophagy. SB216763 inhibited p-Ser/p-Tyr GSK-3α/β and subsequent autophagy. GSK-3β knockdown decreased Cd-induced autophagy. Cd exposure to RH460 cells overexpressed with pcDNA-GSK-3β-HA strongly phosphorylated Ser9/Tyr216 residues and decreased LC3-II. Constitutively active pcDNA-GSK-3β(S9A)-HA overexpression phosphorylated Tyr216 and decreased LC3-II, suggesting that p-Tyr inhibits autophagy. PI3K inhibitors decreased Cd-induced p-Ser GSK-3αβ and LC3-II, whereas a Ser/Thr phosphatase inhibitor, okadaic acid, hyperphosphorylated Ser residues, which accumulated in the nucleus and cytosol, and enhanced LC3-II. The general tyrosine kinase inhibitor genistein suppressed Cd-induced p-Tyr/p-Ser GSK-3α/β and LC3-II. Mouse lung tissues respond to long-term Cd exposure increased p-Tyr, downregulated LC3-II, and accumulated full-length Bax and procaspase-3. Taken together, this study shows that acquired Cd resistance is regulated by GSK-3β phosphorylation state, but not activation state, and intracellular localization of p-Ser GSK-3 regulates Cd-induced autophagy and apoptosis." @default.
• W2159590941 created "2016-06-24" @default.
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• W2159590941 date "2013-07-27" @default.
• W2159590941 modified "2023-10-18" @default.
• W2159590941 title "Serine 9 and Tyrosine 216 Phosphorylation of GSK-3β Differentially Regulates Autophagy in Acquired Cadmium Resistance" @default.
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• W2159590941 doi "https://doi.org/10.1093/toxsci/kft158" @default.
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