Dexamethasone Induces Caspase Activation in Murine Osteoblastic MC3T3-e1 Cells
Document Type
Article
Publication Date
9-23-2003
Description
Glucocorticoids are widely used as anti-inflammatory and chemotherapeutic agents. However, prolonged use of glucocorticoids leads to osteoporosis. This study was designed to examine the mechanism of dexamethasone (DEX)-induced apoptosis in murine osteoblastic MC3T3-E1 cells. Total RNA was extracted from MC3T3-E1 cells treated with 10-7 M DEX for 6 h. DEX exerted a variety of effects on apoptotic gene expression in osteoblasts. Ribonuclease protection assays (RPA) revealed that DEX upregulated mRNA levels of caspases-1, -3, -6, -8, -11, -12, and bcl-XL. Western blot analysis showed enhanced processing of these caspases, with the appearance of their activated enzymes 8 h after DEX treatment. In addition, DEX also induced the activation of caspase-9. DEX elevated the levels of cleaved poly(ADP-ribose) polymerase and lamin A, a caspase-3 and a caspase-6 substrate, respectively. Expression of bcl-XL protein level was upregulated by DEX. Cytochrome c release was detected in the cytosol of DEX-treated cells. Furthermore, caspase-3 enzyme activity was elevated by 2-fold after DEX treatment for 7 h. Finally, early apoptotic cells were detected in cells treated with DEX for 3 h. Our results demonstrate that DEX-induced apoptosis involves gene activation of a number of caspases.
Citation Information
Chua, Chu Chang; Chua, Balvin H.L.; Chen, Zhongyi; Landy, Cathy; and Hamdy, Ronald C.. 2003. Dexamethasone Induces Caspase Activation in Murine Osteoblastic MC3T3-e1 Cells. Biochimica et Biophysica Acta - Molecular Cell Research. Vol.1642(1-2). 79-85. https://doi.org/10.1016/S0167-4889(03)00100-9 PMID: 12972296 ISSN: 0167-4889