Priceman Saul J, Kirzner Jonathan D, Nary Laura J, Morris Devin, Shankar Deepa B, Sakamoto Kathleen M, Medh Rheem D
Department of Biology, California State University at Northridge, Northridge, CA 91330-8303, USA.
Biochem Biophys Res Commun. 2006 Jun 2;344(2):491-9. doi: 10.1016/j.bbrc.2006.03.169. Epub 2006 Apr 5.
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.
糖皮质激素（GC）诱发的T淋巴细胞凋亡之前，细胞内Ca2 +浓度（[Ca2 +] i）会升高，这可能与细胞凋亡有关。本报告表明，GC介导的bZIP转录抑制因子基因E4BP4的上调依赖于[Ca2 +] i水平，并且与GC敏感的CEM - C7 - 14细胞的GC诱发凋亡相关。钙螯合剂EGTA和BAPTA降低了[Ca2 +] i水平，并保护CEM - C7 - 14细胞免受地塞米松（Dex）诱发的E4BP4上调以及凋亡。在GC抗性姐妹克隆CEM - C1 - 15中，Dex处理未诱导[Ca2 +] i水平、E4BP4表达或凋亡，然而，钙离子载体A23187恢复了Dex诱发的E4BP4上调和凋亡。与CEM - C1 - 15细胞相比，CEM - C7 - 14细胞对毒胡萝卜素引起的[Ca2 +] i水平的GC非依赖性升高更敏感，并且E4BP4表达和细胞死亡相应增加，表明[Ca2 +] i水平、E4BP4表达和凋亡之间存在直接相关性。
