The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Distinct Cellular Calcium Metabolism in Radiation-sensitive RKO Human Colorectal Cancer Cells

  • Kim, Yun Tai (Department of Physiology and Biophysics, Inha University College of Medicine) ;
  • Jo, Soo Shin (Department of Physiology and Biophysics, Inha University College of Medicine) ;
  • Park, Young Jun (Department of Physiology and Biophysics, Inha University College of Medicine) ;
  • Lee, Myung Za (Department of Radiation Oncology, Hanyang University College of Medicine) ;
  • Suh, Chang Kook (Department of Physiology and Biophysics, Inha University College of Medicine)
  • Received : 2014.07.21
  • Accepted : 2014.10.13
  • Published : 2014.12.30
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Abstract

Radiation therapy for variety of human solid tumors utilizes mechanism of cell death after DNA damage caused by radiation. In response to DNA damage, cytochrome c was released from mitochondria by activation of pro-apoptotic Bcl-2 family proteins, and then elicits massive $Ca^{2+}$ release from the ER that lead to cell death. It was also suggested that irradiation may cause the deregulation of $Ca^{2+}$ homeostasis and trigger programmed cell death and regulate death specific enzymes. Thus, in this study, we investigated how cellular $Ca^{2+}$ metabolism in RKO cells, in comparison to radiation-resistant A549 cells, was altered by gamma (${\gamma}$)-irradiation. In irradiated RKO cells, $Ca^{2+}$ influx via activation of NCX reverse mode was enhanced and a decline of $[Ca^{2+}]_i$ via forward mode was accelerated. The amount of $Ca^{2+}$ released from the ER in RKO cells by the activation of $IP_3$ receptor was also enhanced by irradiation. An increase in $[Ca^{2+}]_i$ via SOCI was enhanced in irradiated RKO cells, while that in A549 cells was depressed. These results suggest that ${\gamma}$-irradiation elicits enhancement of cellular $Ca^{2+}$ metabolism in radiation-sensitive RKO cells yielding programmed cell death.

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References

  1. Miyashita T, Reed JC. Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell. 1995; 80:293-299. https://doi.org/10.1016/0092-8674(95)90412-3
  2. Oda E, Ohki R, Murasawa H, Nemoto J, Shibue T, Yamashita T, Tokino T, Taniguchi T, Tanaka N. Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science. 2000;288:1053-1058. https://doi.org/10.1126/science.288.5468.1053
  3. Nakano K, Vousden KH. PUMA, a novel proapoptotic gene, is induced by p53. Mol Cell. 2001;7:683-694. https://doi.org/10.1016/S1097-2765(01)00214-3
  4. Li P, Nijhawan D, Budihardjo I, Srinivasula SM, Ahmad M, Alnemri ES, Wang X. Cytochrome c and dATP-dependent formation of Apaf-1/caspase-9 complex initiates an apoptotic protease cascade. Cell. 1997;91:479-489. https://doi.org/10.1016/S0092-8674(00)80434-1
  5. Adams JM, Cory S. The Bcl-2 protein family: arbiters of cell survival. Science. 1998;281:1322-1326. https://doi.org/10.1126/science.281.5381.1322
  6. Hengartner MO. The biochemistry of apoptosis. Nature. 2000; 407:770-776. https://doi.org/10.1038/35037710
  7. Hajnoczky G, Csordas G, Madesh M, Pacher P. Control of apoptosis by IP(3) and ryanodine receptor driven calcium signals. Cell Calcium. 2000;28:349-363. https://doi.org/10.1054/ceca.2000.0169
  8. Pinton P, Ferrari D, Rapizzi E, Di Virgilio F, Pozzan T, Rizzuto R. A role for calcium in Bcl-2 action? Biochimie. 2002;84: 195-201. https://doi.org/10.1016/S0300-9084(02)01373-1
  9. Green DR, Kroemer G. The pathophysiology of mitochondrial cell death. Science. 2004;305:626-629. https://doi.org/10.1126/science.1099320
  10. Pinton P, Rizzuto R. Bcl-2 and $Ca^{2+}$ homeostasis in the endoplasmic reticulum. Cell Death Differ. 2006;13:1409-1418. https://doi.org/10.1038/sj.cdd.4401960
  11. Baffy G, Miyashita T, Williamson JR, Reed JC. Apoptosis induced by withdrawal of interleukin-3 (IL-3) from an IL-3- dependent hematopoietic cell line is associated with repartitioning of intracellular calcium and is blocked by enforced Bcl-2 oncoprotein production. J Biol Chem. 1993;268:6511-6519.
  12. Pinton P, Ferrari D, Magalhães P, Schulze-Osthoff K, Di Virgilio F, Pozzan T, Rizzuto R. Reduced loading of intracellular $Ca^{2+}$ stores and downregulation of capacitative $Ca^{2+}$ influx in Bcl-2-overexpressing cells. J Cell Biol. 2000;148: 857-862. https://doi.org/10.1083/jcb.148.5.857
  13. Foyouzi-Youssefi R, Arnaudeau S, Borner C, Kelley WL, Tschopp J, Lew DP, Demaurex N, Krause KH. Bcl-2 decreases the free $Ca^{2+}$ concentration within the endoplasmic reticulum. Proc Natl Acad Sci U S A. 2000;97:5723-5728. https://doi.org/10.1073/pnas.97.11.5723
  14. Berridge MJ, Lipp P, Bootman MD. The versatility and universality of calcium signalling. Nat Rev Mol Cell Biol. 2000;1:11-21.
  15. Carafoli E, Santella L, Branca D, Brini M. Generation, control, and processing of cellular calcium signals. Crit Rev Biochem Mol Biol. 2001;36:107-260. https://doi.org/10.1080/20014091074183
  16. Trebak M, Bird GS, McKay RR, Putney JW Jr. Comparison of human TRPC3 channels in receptor-activated and storeoperated modes. Differential sensitivity to channel blockers suggests fundamental differences in channel composition. J Biol Chem. 2002;277:21617-21623. https://doi.org/10.1074/jbc.M202549200
  17. Berridge MJ, Bootman MD, Roderick HL. Calcium signalling: dynamics, homeostasis and remodelling. Nat Rev Mol Cell Biol. 2003;4:517-529.
  18. Kirichok Y, Krapivinsky G, Clapham DE. The mitochondrial calcium uniporter is a highly selective ion channel. Nature. 2004;427:360-364. https://doi.org/10.1038/nature02246
  19. Rizzuto R, Pozzan T. Microdomains of intracellular $Ca^{2+}$: molecular determinants and functional consequences. Physiol Rev. 2006;86:369-408. https://doi.org/10.1152/physrev.00004.2005
  20. Roderick HL, Cook SJ. $Ca^{2+}$ signalling checkpoints in cancer: remodelling $Ca^{2+}$ for cancer cell proliferation and survival. Nat Rev Cancer. 2008;8:361-375. https://doi.org/10.1038/nrc2374
  21. Skryma R, Mariot P, Bourhis XL, Coppenolle FV, Shuba Y, Vanden Abeele F, Legrand G, Humez S, Boilly B, Prevarskaya N. Store depletion and store-operated $Ca^{2+}$ current in human prostate cancer LNCaP cells: involvement in apoptosis. J Physiol. 2000;527 Pt 1:71-83. https://doi.org/10.1111/j.1469-7793.2000.00071.x
  22. Chen R, Valencia I, Zhong F, McColl KS, Roderick HL, Bootman MD, Berridge MJ, Conway SJ, Holmes AB, Mignery GA, Velez P, Distelhorst CW. Bcl-2 functionally interacts with inositol 1,4,5-trisphosphate receptors to regulate calcium release from the ER in response to inositol 1,4,5-trisphosphate. J Cell Biol. 2004;166:193-203. https://doi.org/10.1083/jcb.200309146
  23. Zhong F, Davis MC, McColl KS, Distelhorst CW. Bcl-2 differentially regulates $Ca^{2+}$ signals according to the strength of T cell receptor activation. J Cell Biol. 2006;172:127-137. https://doi.org/10.1083/jcb.200506189
  24. Rizzuto R, Pinton P, Ferrari D, Chami M, Szabadkai G, Magalhaes PJ, Di Virgilio F, Pozzan T. Calcium and apoptosis: facts and hypotheses. Oncogene. 2003;22:8619-8627. https://doi.org/10.1038/sj.onc.1207105
  25. Huber SM, Butz L, Stegen B, Klumpp D, Braun N, Ruth P, Eckert F. Ionizing radiation, ion transports, and radioresistance of cancer cells. Front Physiol. 2013;4:212.
  26. Park SI, Park EJ, Kim NH, Baek WK, Lee YT, Lee CJ, Suh CK. Hypoxia delays the intracellular $Ca^{2+}$ clearance by $Na^+$- $Ca^{2+}$ exchanger in human adult cardiac myocytes. Yonsei Med J. 2001;42:333-337. https://doi.org/10.3349/ymj.2001.42.3.333
  27. Kim YT, Park YJ, Jung SY, Seo WS, Suh CK. Effects of $Na^+$- $Ca^{2+}$ exchanger activity on the alpha-amino-3-hydroxy-5-methyl- 4-isoxazolone-propionate-induced $Ca^{2+}$ influx in cerebellar Purkinje neurons. Neuroscience. 2005;131:589-599. https://doi.org/10.1016/j.neuroscience.2004.11.045
  28. Song M, Chen D, Yu SP. The TRPC channel blocker SKF 96365 inhibits glioblastoma cell growth by enhancing reverse mode of the $Na^+$/$Ca^{2+}$ exchanger and increasing intracellular $Ca^{2+}$. Br J Pharmacol. 2014;171:3432-3447. https://doi.org/10.1111/bph.12691
  29. Park HJ, Lyons JC, Ohtsubo T, Song CW. Cell cycle progression and apoptosis after irradiation in an acidic environment. Cell Death Differ. 2000;7:729-738. https://doi.org/10.1038/sj.cdd.4400702
  30. Berridge MJ. The endoplasmic reticulum: a multifunctional signaling organelle. Cell Calcium. 2002;32:235-249. https://doi.org/10.1016/S0143416002001823
  31. Rao RV, Ellerby HM, Bredesen DE. Coupling endoplasmic reticulum stress to the cell death program. Cell Death Differ. 2004;11:372-380. https://doi.org/10.1038/sj.cdd.4401378
  32. Elliott AC. Recent developments in non-excitable cell calcium entry. Cell Calcium. 2001;30:73-93. https://doi.org/10.1054/ceca.2001.0215
  33. Putney JW Jr, Broad LM, Braun FJ, Lievremont JP, Bird GS. Mechanisms of capacitative calcium entry. J Cell Sci. 2001; 114:2223-2229.
  34. Scorrano L, Oakes SA, Opferman JT, Cheng EH, Sorcinelli MD, Pozzan T, Korsmeyer SJ. BAX and BAK regulation of endoplasmic reticulum $Ca^{2+}$: a control point for apoptosis. Science. 2003;300:135-139. https://doi.org/10.1126/science.1081208
  35. Urashima T, Wang K, Adelstein SJ, Kassis AI. Activation of diverse pathways to apoptosis by (125)IdUrd and gammaphoton exposure. Int J Radiat Biol. 2004;80:867-874. https://doi.org/10.1080/09553000400017655
  36. Kim NH, Park KS, Sohn JH, Yeh BI, Ko CM, Kong ID. Functional Expression of P2Y Receptors in WERI-Rb1 Retinoblastoma Cells. Korean J Physiol Pharmacol. 2011;15: 61-66. https://doi.org/10.4196/kjpp.2011.15.1.61

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