Biochemical and Biophysical Research Communications, Vol.344, No.2, 491-499, 2006
Calcium-dependent upregulation of E4BP4 expression correlates with glucocorticoid-evoked apoptosis of human leukemic CEM cells
Glucocorticoid (GC)-evoked apoptosis of T-lymphoid cells is preceded by increases in the intracellular Ca2+ concentration ([Ca2+](i)), which may contribute to apoptosis. This report demonstrates that GC-mediated upregulation of the bZIP transcriptional repressor gene, E4BP4, is dependent on [Ca2+](i) levels, and correlates with GC-evoked apoptosis of GC-sensitive CEM-C7-14 cells. Calcium chelators EGTA and BAPTA reduced [Ca2+](i) levels and protected CEM-C7-14 cells from Dex-evoked E4BP4 upregulation as well as apoptosis. In the GC-resistant sister clone, CEM-Cl-15, Dex treatment did not induce [Ca2+](i) levels, E4BP4 expression or apoptosis, however, the calcium ionophore A23187 restored Dex-evoked E4BP4 upregulation and apoptosis. CEM-C7-14 cells were more sensitive to GC-independent increases in [Ca2+](i) levels by thapsigargin, and a corresponding increase in E4BP4 expression and cell death, compared to CEM-Cl-15 cells, suggesting a direct correlation between [Ca2+](i) levels, E4BP4 expression, and apoptosis. (c) 2006 Elsevier Inc. All rights reserved.