Recent insights into the mechanism of glucocorticosteroid-induced apoptosis.
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.
Distelhorst
C W
CW
Division of Hematology/Oncology and Comprehensive Cancer Center, Departments of Medicine and Pharmacology, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, OH 44106-4937, USA. cwd@po.cwru.edu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020169:Caspases / Q000378:metabolism*; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D007938:Leukemia / Q000378:metabolism; D008223:Lymphoma / Q000378:metabolism; D008928:Mitochondria / Q000502:physiology*; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*
D005938:Glucocorticoids; D009097:Multienzyme Complexes; D019253:Proto-Oncogene Proteins c-bcl-2; D020169:Caspases; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex