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On the link between Bcl‐2 family proteins and glucocorticoid‐induced apoptosis
Author(s) -
Almawi Wassim Y.,
Melemedjian Ohannes K.,
Jaoude Maroun M. Abou
Publication year - 2004
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0903450
Subject(s) - apoptosis , biology , bcl 2 family , microbiology and biotechnology , bcl xl , inhibitor of apoptosis domain , programmed cell death , signal transduction , mitochondrion , glucocorticoid receptor , inhibitor of apoptosis , phosphorylation , caspase , glucocorticoid , immunology , biochemistry
As immunosuppressive agents, glucocorticoids (GCs) act by inhibiting the expression of cytokines and adhesion molecules at the transcriptional and post‐transcriptional levels. In addition, GCs exerted their effects by modulating apoptosis. In view of the central role of the Bcl‐2 family protein in regulating apoptosis, it was tempting to speculate that GCs modulated apoptosis through modulation of the expression of proapoptotic (Bax, Bcl‐X S , Bak) and prosurvival (Bcl‐2, Bcl‐X L , Bcl‐w) Bcl‐2 family members. Prosurvival Bcl‐2 family members in various cell types antagonized GC‐induced apoptosis, thereby suggesting a causal relationship between GC‐induced apoptosis and Bcl‐2 proteins. The antagonism of apoptosis afforded by prosurvival Bcl‐2 proteins appeared to be specific for the GCs, as Bcl‐2 and Bcl‐x L blocked GC‐induced apoptosis in T cell hybridomas but did not affect Fas or activation‐induced apoptosis. Although it is speculated that GC‐induced apoptosis may be mediated through the activation of proapoptotic Bcl‐2 proteins, recent findings suggest that this may vary depending on the conditions and the cell types used. The mechanism by which Bcl‐2 inhibited GC‐induced apoptosis remains uncertain. It was suggested that Bcl‐2 acted on outer mitochondrial membranes to preserve their function. Bcl‐2 overexpression also inhibited GC‐induced apoptotic events, including caspase activation and mitochondrial dysfunction. The cross‐talk of the GC receptors with other secondary messengers could lead to modulation of the activity of Bcl‐2 proteins through modification of their phosphorylation status, without ruling out the possibility of a physical interaction between activated GR with Bcl‐2 proteins.