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CHANGING OF RGS TRANSCRIPTS LEVELS BY LOW-DOSE-RATE IONIZING RADIATION IN MOUSE TESTIS

  • Kim, Tae-Hwan (Laboratory of Veterinary Pathology, College of Veterinary Medicine, Kyungpook National University) ;
  • Baik, Ji Sue (Research Center, Dongnam Institute of Radiological & Medical Sciences) ;
  • Heo, Kyu (Research Center, Dongnam Institute of Radiological & Medical Sciences) ;
  • Kim, Joong Sun (Research Center, Dongnam Institute of Radiological & Medical Sciences) ;
  • Lee, Ki Ja (Laboratory of Veterinary Physiology and Cell Signaling, College of Veterinary Medicine, Kyungpook National University) ;
  • Rhee, Man Hee (Laboratory of Veterinary Physiology and Cell Signaling, College of Veterinary Medicine, Kyungpook National University) ;
  • Kim, Sung Dae (Research Center, Dongnam Institute of Radiological & Medical Sciences)
  • Received : 2015.07.20
  • Accepted : 2015.09.08
  • Published : 2015.09.30

Abstract

Deleterious effects of high dose radiation exposure with high-dose-rate are unarguable, but they are still controversial in low-dose-rate. The regulator of G-protein signaling (RGS) is a negative regulator of G protein-coupled receptor (GPCR) signaling. In addition, it is reported that irradiation stress led to GPCR-mediated mitogen-activated protein kinase (MAPK) and phosphotidylinositol 3-kinase (PI3-k) signaling. The RGS mRNA expression profiles by whole body radiation with low-dose-rate has not yet been explored. In the present study, we, therefore, examined which RGS was modulated by the whole body radiation with low-dose-rate ($3.49mGy{\cdot}h^{-1}$). Among 16 RGS expression tested, RGS6, RGS13 and RGS16 mRNA were down-regulated by low-dose-rate irradiation. This is the first report that whole body radiation with low-dose-rate can modulate the different RGS expression levels. These results are expected to reveal the potential target and/or the biomarker proteins associated with male testis toxicity induced by low-dose-rate irradiation, which might contribute to understanding the mechanism beyond the testis toxicity.

Keywords

References

  1. Endale M, Kim SD, Lee WM, Kim S, Suk K, Cho JY, Park HJ, Wagly Y, Kim S, Oh JW, Rhee MH. Ischemia induces regulator of G protein signaling 2 (RGS2) protein upregulation and enhances apoptosis in astrocytes. Am J Physiol Cell Physiol. 2010; 298(3):C611-23. https://doi.org/10.1152/ajpcell.00517.2008
  2. Iwaki S, Lu Y, Xie Z, Druey KM. p53 negatively regulates RGS13 protein expression in immune cells. 2011;286(25):22219-26. https://doi.org/10.1074/jbc.M111.228924
  3. Maity B, Stewart A, O'Malley Y, Askeland RW, Sugg SL, Fisher RA. Regulator of G protein signaling 6 is a novel suppressor of breast tumor initiation and progression. Carcinogenesis. 2013; 34(8):1747-55. https://doi.org/10.1093/carcin/bgt128
  4. Hepler JR. RGS protein and G protein interactions: a little help from their friends. Mol Pharmacol. 2003;64(3):547-9. https://doi.org/10.1124/mol.64.3.547
  5. Druey KM. Bridging with GAPs: receptor communication through RGS proteins. Sci STKE. 2001 ;2001(104):re14.
  6. Hendriks-Balk MC, Peters SL, Michel MC, Alewijnse AE. Regulation of G protein-coupled receptor signalling: focus on the cardiovascular system and regulator of G protein signalling proteins. Eur J Pharmacol. 2008;585(2-3):278-91. https://doi.org/10.1016/j.ejphar.2008.02.088
  7. Hollinger S, Hepler JR. Cellular regulation of RGS proteins: modulators and integrators of G protein signaling. Pharmacol Rev. 2002;54(3):527-59. https://doi.org/10.1124/pr.54.3.527
  8. Abramow-Newerly M, Roy AA, Nunn C, Chidiac P. RGS proteins have a signalling complex: interactions between RGS proteins and GPCRs, effectors, and auxiliary proteins. Cell Signal. 2006; 18(5):579-91. https://doi.org/10.1016/j.cellsig.2005.08.010
  9. Kach J, Sethakorn N, Dulin NO. A finer tuning of G-protein signaling through regulated control of RGS proteins. Am J Physiol Heart Circ Physiol. 2012;303(1):H19-35. https://doi.org/10.1152/ajpheart.00764.2011
  10. Ross EM, Wilkie TM. GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins. Annu Rev Biochem. 2000;69:795-827. https://doi.org/10.1146/annurev.biochem.69.1.795
  11. Ishii M, Kurachi Y. Physiological actions of regulators of G-protein signaling (RGS) proteins. Life Sci. 2003;74(2-3):163-71. https://doi.org/10.1016/j.lfs.2003.09.004
  12. Nguyen CH, Zhao P, Sobiesiak AJ, Chidiac P. RGS2 is a component of the cellular stress response. Biochem Biophys Res Commun. 2012; 426(1): 129-34. https://doi.org/10.1016/j.bbrc.2012.08.050
  13. Ip AK, Tso PH, Lee MM, Wong YH. Elevated expression of RGS19 impairs the responsiveness of stress-activated protein kinases to serum. Mol Cell Biochem. 2012;362(1-2):159-68. https://doi.org/10.1007/s11010-011-1138-1
  14. Hidvegi T, Mirnics K, Hale P, Ewing M, Beckett C, Perlmutter DH. Regulator of G Signaling 16 is a marker for the distinct endoplasmic reticulum stress state associated with aggregated mutant alpha1- antitrypsin Z in the classical form of alpha1- antitrypsin deficiency. J Biol Chem. 2007; 282(38):27769-80. https://doi.org/10.1074/jbc.M704330200
  15. Miyoshi N, Ishii H, Sekimoto M, Doki Y, Mori M. RGS16 is a marker for prognosis in colorectal cancer. Ann Surg Oncol. 2009;16(12):3507-14. https://doi.org/10.1245/s10434-009-0690-3
  16. Kim JH, Lee JY, Lee KT, Lee JK, Lee KH, Jang KT, Heo JS, Choi SH, Rhee JC. RGS16 and FosB underexpressed in pancreatic cancer with lymph node metastasis promote tumor progression. Tumour Biol. 2010;31(5):541-8. https://doi.org/10.1007/s13277-010-0067-z
  17. Silini A, Ghilardi C, Figini S, Sangalli F, Fruscio R, Dahse R, Pedley RB, Giavazzi R, Bani M. Regulator of G-protein signaling 5 (RGS5) protein: a novel marker of cancer vasculature elicited and sustained by the tumor's proangiogenic microenvironment. Cell Mol Life Sci. 2012;69(7): 1167-78. https://doi.org/10.1007/s00018-011-0862-8
  18. Rangel J, Nosrati M, Leong SP, Haqq C, Miller JR, 3rd, Sagebiel RW, Kashani-Sabet M. Novel role for RGS1 in melanoma progression. Am J Surg Pathol. 2008;32(8):1207-12. https://doi.org/10.1097/PAS.0b013e31816fd53c
  19. Donnelly EH, Nemhauser JB, Smith JM, Kazzi ZN, Farfan EB, Chang AS, Naeem SF. Acute radiation syndrome: assessment and management. South Med J. 2010;103(6):541-6. https://doi.org/10.1097/SMJ.0b013e3181ddd571
  20. van Baardwijk A, Tome WA, van Elmpt W, Bentzen SM, Reymen B, Wanders R, Houben R, Ollers M, Lambin P, De Ruysscher D. Is high-dose stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC) overkill? A systematic review. Radiother Oncol. 2012;105(2): 145-9. https://doi.org/10.1016/j.radonc.2012.09.008
  21. Gong EJ, Shin IS, Son TG, Yang K, Heo K, Kim JS. Low-dose-rate radiation exposure leads to testicular damage with decreases in DNMT1 and HDAC1 in the murine testis. J Radiat Res. 2014; 55(1):54-60. https://doi.org/10.1093/jrr/rrt090
  22. De Vries L, Zheng B, Fischer T, Elenko E, Farquhar MG. The regulator of G protein signaling family. Annu Rev Pharmacol Toxicol. 2000;40: 235-71. https://doi.org/10.1146/annurev.pharmtox.40.1.235
  23. Hooks SB, Waldo GL, Corbitt J, Bodor ET, Krumins AM, Harden TK. RGS6, RGS7, RGS9, and RGS11 stimulate GTPase activity of Gi family G-proteins with differential selectivity and maximal activity. J Biol Chem. 2003;278(12):10087-93. https://doi.org/10.1074/jbc.M211382200
  24. Chatterjee TK, Fisher RA. Mild heat and proteotoxic stress promote unique subcellular trafficking and nucleolar accumulation of RGS6 and other RGS proteins. Role of the RGS domain in stressinduced trafficking of RGS proteins. J Biol Chem. 2003;278(32):30272-82. https://doi.org/10.1074/jbc.M212688200
  25. Huang J, Yang J, Maity B, Mayuzumi D, Fisher RA. Regulator of G protein signaling 6 mediates doxorubicin-induced ATM and p53 activation by a reactive oxygen species-dependent mechanism. Cancer Res. 2011;71(20):6310-9. https://doi.org/10.1158/0008-5472.CAN-10-3397
  26. Maity B, Stewart A, O'Malley Y, Askeland RW, Sugg SL, Fisher RA. Regulator of G protein signaling 6 is a novel suppressor of breast tumor initiation and progression. Carcinogenesis. 2013; 34(8):1747-55. https://doi.org/10.1093/carcin/bgt128
  27. Liu Z, Fisher RA. RGS6 interacts with DMAP1 and DNMT1 and inhibits DMAP1 transcriptional repressor activity. J Biol Chem. 2004;279(14): 14120-8. https://doi.org/10.1074/jbc.M309547200
  28. Johnson EN, Druey KM. Functional characterization of the G protein regulator RGS13. J Biol Chem. 2002;277(19):16768-74. https://doi.org/10.1074/jbc.M200751200
  29. Xie Z, Geiger TR, Johnson EN, Nyborg JK, Druey KM. RGS13 acts as a nuclear repressor of CREB. Mol Cell. 2008;31(5):660-70. https://doi.org/10.1016/j.molcel.2008.06.024
  30. Xie Z, Yang Z, Druey KM. Phosphorylation of RGS13 by the cyclic AMP-dependent protein kinase inhibits RGS13 degradation. J Mol Cell Biol. 2010;2(6):357-65. https://doi.org/10.1093/jmcb/mjq031
  31. Iwaki S, Lu Y, Xie Z, Druey KM. p53 Negatively Regulates RGS13 Protein Expression in Immune Cells. J Biol Chem. 2011;286(25):22219-26. https://doi.org/10.1074/jbc.M111.228924
  32. Chen CK, Wieland T, Simon MI. RGS-r, a retinal specific RGS protein, binds an intermediate conformation of transducin and enhances recycling. Proc Natl Acad Sci U S A. 1996;93(23): 12885-9. https://doi.org/10.1073/pnas.93.23.12885
  33. Beadling C, Druey KM, Richter G, Kehrl JH, Smith KA. Regulators of G protein signaling exhibit distinct patterns of gene expression and target G protein specificity in human lymphocytes. J Immunol. 1999;162(5):2677-82.
  34. Xu X, Zeng W, Popov S, Berman DM, Davignon I, Yu K, Yowe D, Offermanns S, Muallem S, Wilkie TM. RGS proteins determine signaling specificity of Gq-coupled receptors. J Biol Chem. 1999;274(6):3549-56. https://doi.org/10.1074/jbc.274.6.3549
  35. Miyoshi N, Ishii H, Sekimoto M, Doki Y, Mori M. RGS16 is a marker for prognosis in colorectal cancer. Ann Surg Oncol. 2009;16(12):3507-14. https://doi.org/10.1245/s10434-009-0690-3

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