Dexamethasone-induced apoptosis and up-regulation of Bim is dependent on glycogen synthase kinase-3.
2009
Abstract Glucocorticoids are commonly used in the treatment of lymphoid malignancies. In this study, we show that apoptosis induced by dexamethasone (Dex), a synthetic glucocorticoid, was dependent on mitochondria, since overexpression of Bcl-X L prevented Dex-induced apoptotic changes. Dominant negative (DN) caspase-9 also prevented Dex-induced apoptotic changes including the loss of mitochondrial membrane potential indicating that caspase-9 controls mitochondrial changes. In addition, we evaluated the role of glycogen synthase kinase (GSK3) in Dex-induced apoptosis. Inhibition of GSK3 attenuated Dex-induced up-regulation of Bim, loss of mitochondrial membrane potential, release of cyt c and DNA fragmentation. These results indicate that GSK3 contributes to Dex-induced apoptosis by controlling up-regulation of Bim.
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