Recent insights into the mechanism of glucocorticosteroid-induced apoptosis

被引:245
作者
Distelhorst, CW
机构
[1] Case Western Reserve Univ, Div Hematol Oncol, Cleveland, OH 44106 USA
[2] Case Western Reserve Univ, Sch Med, Ctr Comprehens Canc, Dept Med, Cleveland, OH 44106 USA
[3] Case Western Reserve Univ, Sch Med, Ctr Comprehens Canc, Dept Pharmacol, Cleveland, OH 44106 USA
[4] Univ Hosp Cleveland, Cleveland, OH 44106 USA
关键词
glucocorticosteroid; dexamethasone; apoptosis; leukemia; lymphoma;
D O I
10.1038/sj.cdd.4400969
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
Glucocorticosteroid hormones induce apoptosis in lymphocytes. Therefore, glucocorticoids are commonly used as Immunosuppressive and chemotherapeutic agents. This review examines many facets of the process by which glucocorticoids induce apoptosis. This process is divided into three stages, an initiation stage that involves glucocorticoid receptor-mediated gene regulation, a decision stage that Involves the counterbalancing influence of prosurvival and proapoptotic factors, and the execution stage which involves caspase and endonuclease activation. Many aspects of glucocorticoid-induced apoptosis, such as mitochondrial dysfunction and caspase activation, are important steps in virtually all forms of apoptosis. But the process glucocorticoid-induced apoptosis differs from other forms of apoptosis in terms of initiation at the transcriptional level and involvement of the multicatalytic proteasome and calcium. Moreover, the abundant opportunity for crosstalk between the glucocorticoid receptor and other signaling pathways Increases the complexity of glucocorticoid-induced apoptosis and its regulation.
引用
收藏
页码:6 / 19
页数:14
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