Dexamethasone induces caspase activation in murine osteoblastic MC3T3-E1 cells

被引:57
作者
Chua, CC
Chua, BHL
Chen, ZY
Landy, C
Hamdy, RC
机构
[1] E Tennessee State Univ, Osteoporosis Ctr, James H Quillen Coll Med, Johnson City, TN 37614 USA
[2] Vet Affairs Med Ctr, Johnson City, TN 37614 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH | 2003年 / 1642卷 / 1-2期
关键词
dexamethasone; caspase; apoptosis; osteoblast;
D O I
10.1016/S0167-4889(03)00100-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 marine 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-X-L. 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(ADPribose) 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. (C) 2003 Elsevier B.V. All rights reserved.
引用
收藏
页码:79 / 85
页数:7
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