Susceptibility of CEM Cell Clones to GC-Evoked ApoptosisCEM细胞克隆诱发细胞凋亡的GC敏感性.ppt

ROLE OF INTRACELLULAR CALCIUM IN GLUCOCORTICOID-EVOKED LYMPHOID CELL APOPTOSIS,Devin Morris California State University, Northridge,Apoptosis,Development Homeostasis Disease,Physiological roles of apoptosis,Glucocorticoid Pathway,Susceptibility of CEM Cell Clones to GC-Evoked Apoptosis,GC-induced Increase in Intracellular Calcium in GC-Susceptible CEM cells,Time- & GC-Dose-Dependent Increase in Ca+2i in CEM-C7-14 Cells,Modulators of Ca+2i Levels Influence GC-Evoked Death of CEM Cells,EGTA Suppresses GC-Evoked Increase in Ca+2i Levels in CEM-C7-14 Cells,Glucocorticoid Signaling Pathway,Pathway Inhibitors,Normal Pathway,Inhibition of Calmodulin Protects CEM-C7-14 Cells from GC-evoked Death,Inhibition of Calmodulin Kinase II Protects CEM-C7-14 Cells from GC-evoked Death,Inhibition of Calcineurin Protects CEM-C7-14 Cells from GC-evoked Death,Conclusions,GCs increase Ca+2i levels only in the GC-susceptible CEM-C7-14 cell line in a dose dependent manner; not in the GC-resistant sister cell line, CEM-C1-15. Calcium chelation by either BAPTA or EGTA protected CEM-C7-14 cells from GC-evoked apoptosis, in conjunction with a reduction in the amount of free Ca+2i. The calcium ionophore A23187 causes sensitization of CEM-C1-15 cells to GC-evoked apoptosis. Inhibition of calmodulin, calmodulin kinase II or calcineurin, all intermediates in the calcium signaling pathway, impart varying degrees of protection to CEM-C7-14 cells from GC-evoked apoptosis. Our data demonstrate a clear correlation between calcium signaling and GC-evoked apoptosis,Future Goals,Further studies will aim to understand Ca+2-dependent changes in gene regulation that contribute to apoptosis. Candidate genes such as the transcriptional repressor E4BP4, and its downstream targets are being studied. Our ultimate goal is to understand the molecular pathway for apoptosis in T-lymphoid cells as well as in other physiologically relevant models for apoptosis, such as osteoblasts, keratinocytes and macrophages.,Acknowledgements,Funded by grants from the NIH MBRS-SCORE Program, the CSUN Office of Graduate Studies, Research and International Programs, and the