Molecular Endocrinology, Vol 7, 686-693, Copyright © 1993 by Endocrine Society

ARTICLES

Effect of glucocorticosteroid treatment on intracellular calcium homeostasis in mouse lymphoma cells

M Lam, G Dubyak and CW Distelhorst
Ireland Cancer Center, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4937.

There is growing evidence for the involvement of Ca2+ in the programmed cell death (apoptosis) of lymphocytes, but the nature of glucocorticoid- induced Ca2+ fluxes and their role in the cell death pathway are poorly understood. In the study reported here, we assessed the effect of glucocorticoid treatment on intracellular Ca2+ homeostasis in W7MG1 mouse lymphoma cells. Levels of cytosolic Ca2+ were measured using the intracellular Ca2+ indicator fura2 AM, and total cellular Ca2+ was measured by atomic absorbance spectroscopy. The level of Ca2+ within internal stores, including the endoplasmic reticulum (ER), was estimated by measuring the increase in cytosolic Ca2+ induced by either ionomycin, an ionophore that mobilizes Ca2+ from a variety of internal stores, and by thapsigargin, a specific inhibitor of the ER-associated Ca(2+)-ATPase that mobilizes Ca2+ from the ER. Glucocorticoid treatment induced a significant decrease in ionomycin- and thapsigargin- mobilizable Ca2+ stores that was accompanied by an initial decrease in total cellular Ca2+, followed by a modest increase in both total cellular Ca2+ and cytosolic Ca2+. The glucocorticoid-induced depletion of internal Ca2+ stores was receptor mediated and occurred after a delay corresponding to the time required for glucocorticoid receptor complexes to regulate gene transcription. Mobilization of ER-associated Ca2+ stores by thapsigargin treatment induced DNA fragmentation and cell death similar to that observed after glucocorticoid treatment. These findings suggest that a mobilization of Ca2+ from internal stores may be a critical step in the apoptotic pathway of mouse lymphoma cells.

This article has been cited by other articles:

				M. W. Harr, Y. Rong, M. D. Bootman, H. L. Roderick, and C. W. Distelhorst Glucocorticoid-mediated Inhibition of Lck Modulates the Pattern of T Cell Receptor-induced Calcium Signals by Down-regulating Inositol 1,4,5-Trisphosphate Receptors J. Biol. Chem., November 13, 2009; 284(46): 31860 - 31871. [Abstract] [Full Text] [PDF]

				M. C. Davis, K. S. McColl, F. Zhong, Z. Wang, M. H. Malone, and C. W. Distelhorst Dexamethasone-induced Inositol 1,4,5-Trisphosphate Receptor Elevation in Murine Lymphoma Cells Is Not Required for Dexamethasone-mediated Calcium Elevation and Apoptosis J. Biol. Chem., April 18, 2008; 283(16): 10357 - 10365. [Abstract] [Full Text] [PDF]

				A. B. Parekh and J. W. Putney Jr. Store-Operated Calcium Channels Physiol Rev, April 1, 2005; 85(2): 757 - 810. [Abstract] [Full Text] [PDF]

				M. H. Malone, Z. Wang, and C. W. Distelhorst The Glucocorticoid-induced Gene tdag8 Encodes a Pro-apoptotic G Protein-coupled Receptor Whose Activation Promotes Glucocorticoid-induced Apoptosis J. Biol. Chem., December 17, 2004; 279(51): 52850 - 52859. [Abstract] [Full Text] [PDF]

				B.-C. Kim, H.-T. Kim, M. Mamura, I. S. Ambudkar, K.-S. Choi, and S.-J. Kim Tumor Necrosis Factor Induces Apoptosis in Hepatoma Cells by Increasing Ca2+ Release from the Endoplasmic Reticulum and Suppressing Bcl-2 Expression J. Biol. Chem., August 23, 2002; 277(35): 31381 - 31389. [Abstract] [Full Text] [PDF]

				S. Greenstein, K. Ghias, N. L. Krett, and S. T. Rosen Mechanisms of Glucocorticoid-mediated Apoptosis in Hematological Malignancies Clin. Cancer Res., June 1, 2002; 8(6): 1681 - 1694. [Abstract] [Full Text] [PDF]

				L. K. Nutt, J. Chandra, A. Pataer, B. Fang, J. A. Roth, S. G. Swisher, R. G. O'Neil, and D. J. McConkey Bax-mediated Ca2+ Mobilization Promotes Cytochrome c Release during Apoptosis J. Biol. Chem., May 31, 2002; 277(23): 20301 - 20308. [Abstract] [Full Text] [PDF]

				L. K. Nutt, A. Pataer, J. Pahler, B. Fang, J. Roth, D. J. McConkey, and S. G. Swisher Bax and Bak Promote Apoptosis by Modulating Endoplasmic Reticular and Mitochondrial Ca2+ Stores J. Biol. Chem., March 8, 2002; 277(11): 9219 - 9225. [Abstract] [Full Text] [PDF]

				M. Unkila, K. S. McColl, M. J. Thomenius, K. Heiskanen, and C. W. Distelhorst Unreliability of the Cytochrome c-Enhanced Green Fluorescent Fusion Protein as a Marker of Cytochrome c Release in Cells That Overexpress Bcl-2 J. Biol. Chem., October 12, 2001; 276(42): 39132 - 39137. [Abstract] [Full Text] [PDF]

				S. Jayadev, J. C. Barrett, and E. Murphy Elevated ceramide is downstream of altered calcium homeostasis in low serum-induced apoptosis Am J Physiol Cell Physiol, November 1, 2000; 279(5): C1640 - C1647. [Abstract] [Full Text] [PDF]

				K. Nakamura, E. Bossy-Wetzel, K. Burns, M. P. Fadel, M. Lozyk, I. S. Goping, M. Opas, R. C. Bleackley, D. R. Green, and M. Michalak Changes in Endoplasmic Reticulum Luminal Environment Affect Cell Sensitivity to Apoptosis J. Cell Biol., August 21, 2000; 150(4): 731 - 740. [Abstract] [Full Text] [PDF]

				A. A Gutierrez, J. M. Arias, L. Garcia, J. Mas-Oliva, and A. Guerrero-Hernandez Activation of a Ca2+-permeable cation channel by two different inducers of apoptosis in a human prostatic cancer cell line J. Physiol., May 15, 1999; 517(1): 95 - 107. [Abstract] [Full Text] [PDF]

				K. Imaizumi, T. Morihara, Y. Mori, T. Katayama, M. Tsuda, T. Furuyama, A. Wanaka, M. Takeda, and M. Tohyama The Cell Death-promoting Gene DP5, Which Interacts with the BCL2 Family, Is Induced during Neuronal Apoptosis Following Exposure to Amyloid beta  Protein J. Biol. Chem., March 19, 1999; 274(12): 7975 - 7981. [Abstract] [Full Text] [PDF]

				S. Jayadev, J. G. Petranka, S. K. Cheran, J. A. Biermann, J. C. Barrett, and E. Murphy Reduced Capacitative Calcium Entry Correlates with Vesicle Accumulation and Apoptosis J. Biol. Chem., March 19, 1999; 274(12): 8261 - 8268. [Abstract] [Full Text] [PDF]

				J. P Gardner and L. Zhang Glucocorticoid modulation of Ca2+ homeostasis in human B lymphoblasts J. Physiol., January 15, 1999; 514(2): 385 - 396. [Abstract] [Full Text] [PDF]

				H. He, X.-M. Qi, J. Grossmann, and C. W. Distelhorst c-Fos Degradation by the Proteasome. AN EARLY, Bcl-2-REGULATED STEP IN APOPTOSIS J. Biol. Chem., September 25, 1998; 273(39): 25015 - 25019. [Abstract] [Full Text] [PDF]

				C. W. Distelhorst and G. Dubyak Role of Calcium in Glucocorticosteroid-Induced Apoptosis of Thymocytes and Lymphoma Cells: Resurrection of Old Theories by New Findings Blood, February 1, 1998; 91(3): 731 - 734. [Full Text] [PDF]

				M. B. Bhat, J. Zhao, W. Zang, C. W. Balke, H. Takeshima, W. G. Wier, and J. Ma Caffeine-induced Release of Intracellular Ca2+ from Chinese Hamster Ovary Cells Expressing Skeletal Muscle Ryanodine Receptor: Effects on Full-Length and Carboxyl-Terminal Portion of Ca2+Release Channels J. Gen. Physiol., December 1, 1997; 110(6): 749 - 762. [Abstract] [Full Text] [PDF]

				Q. Guo, B. L. Sopher, K. Furukawa, D. G. Pham, N. Robinson, G. M. Martin, and M. P. Mattson Alzheimer's Presenilin Mutation Sensitizes Neural Cells to Apoptosis Induced by Trophic Factor Withdrawal and Amyloid beta -Peptide: Involvement of Calcium and Oxyradicals J. Neurosci., June 1, 1997; 17(11): 4212 - 4222. [Abstract] [Full Text] [PDF]

				J. E. Reynolds and A. Eastman Intracellular Calcium Stores Are Not Required for Bcl-2-mediated Protection from Apoptosis J. Biol. Chem., November 1, 1996; 271(44): 27739 - 27743. [Abstract] [Full Text] [PDF]

				A. B. Scoltock, C. D. Bortner, G. St. J. Bird, J. W. Putney Jr., and J. A. Cidlowski A Selective Requirement for Elevated Calcium in DNA Degradation, but Not Early Events in Anti-Fas-induced Apoptosis J. Biol. Chem., September 22, 2000; 275(39): 30586 - 30596. [Abstract] [Full Text] [PDF]