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-C1-15, 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-C1-15 cells, suggesting a direct correlation between [Ca2+]i levels, E4BP4 expression, and apoptosis.
Priceman
Saul J
SJ
Department of Biology, California State University at Northridge, Northridge, CA 91330-8303, USA.
Kirzner
Jonathan D
JD
Nary
Laura J
LJ
Morris
Devin
D
Shankar
Deepa B
DB
Sakamoto
Kathleen M
KM
Medh
Rheem D
RD
D017209:Apoptosis / Q000187:drug effects*; D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D007945:Leukemia, Lymphoid / Q000378:metabolism* / Q000473:pathology*; D013223:Statistics as Topic; D015854:Up-Regulation / Q000187:drug effects
D050976:Basic-Leucine Zipper Transcription Factors; D005938:Glucocorticoids; C497440:NFIL3 protein, human; D002118:Calcium