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Expression Pattern of the Thioredoxin System in Human Endothelial Progenitor Cells and Endothelial Cells Under Hypoxic Injury

  • Park, Keon-Jae (Division of Cardiology, Department of Internal Medicine, Chungbuk National University School of Medicine) ;
  • Kim, Yeon-Jeong (Division of Cardiology, Department of Internal Medicine, Chungbuk National University School of Medicine) ;
  • Choi, Eun-Ju (Division of Cardiology, Department of Internal Medicine, Chungbuk National University School of Medicine) ;
  • Park, No-Kwan (Division of Cardiology, Department of Internal Medicine, Chungbuk National University School of Medicine) ;
  • Kim, Gi-Hyun (Division of Cardiology, Department of Internal Medicine, Chungbuk National University School of Medicine) ;
  • Kim, Sang-Min (Division of Cardiology, Department of Internal Medicine, Chungbuk National University School of Medicine) ;
  • Lee, Sang-Yeub (Division of Cardiology, Department of Internal Medicine, Chungbuk National University School of Medicine) ;
  • Bae, Jng-Whan (Division of Cardiology, Department of Internal Medicine, Chungbuk National University School of Medicine) ;
  • Hwang, Kyung-Kuk (Division of Cardiology, Department of Internal Medicine, Chungbuk National University School of Medicine) ;
  • Kim, Dong-Woon (Division of Cardiology, Department of Internal Medicine, Chungbuk National University School of Medicine) ;
  • Cho, Myeong-Chan (Division of Cardiology, Department of Internal Medicine, Chungbuk National University School of Medicine)
  • Received : 2010.05.09
  • Accepted : 2010.08.09
  • Published : 2010.12.30

Abstract

Background and Objectives: The thioredoxin (TRx) system is a ubiquitous thiol oxidoreductase pathway that regulates cellular reduction/oxidation status. Although endothelial cell (EC) hypoxic damage is one of the important pathophysiologic mechanisms of ischemic heart disease, its relationship to the temporal expression pattern of the TRx system has not yet been elucidated well. The work presented here was performed to define the expression pattern of the TRx system and its correlation with cellular apoptosis in EC lines in hypoxic stress. These results should provide basic clues for applying aspects of the TRx system as a therapeutic molecule in cardiovascular diseases. Subjects and Methods: Hypoxia was induced with 1% O$_2$, generated in a BBL GasPak Pouch (Becton Dickinson, Franklin Lakes, NJ, USA) in human endothelial progenitor cells (hEPC) and human umbilical vein endothelial cells (HUVEC). Apoptosis of these cells was confirmed by Annexin-V: Phycoerythrin flow cytometry. Expression patterns of TRx; TRx reductase; TRx interacting protein; and survival signals, such as Bcl-2 and Bax, in ECs under hypoxia were checked. Results: Apoptosis was evident after hypoxia in the two cell types. Higher TRx expression was observed at 12 hours after hypoxia in hEPCs and 12, 36, 72 hours of hypoxia in HUVECs. The expression patterns of the TRx system components showed correlation with EC apoptosis and cell survival markers. Conclusion: Hypoxia induced significant apoptosis and its related active changes of the TRx system were evident in human EC lines. If the cellular impact of TRx expression pattern in various cardiovascular tissues under hypoxia or oxidative stress was studied meticulously, the TRx system could be applied as a new therapeutic target in cardiovascular diseases, such as ischemic heart disease or atherosclerosis.

Keywords

References

  1. Melley DD, Evans TW, Quinlan GJ. Redox regulation of neutrophil apoptosis and the systemic inflammatory response syndrome. Clin Sci 2005;108:413-24. https://doi.org/10.1042/CS20040228
  2. Krohn K, Maier J, Paschke R. Mechanism of disease: hydrogen peroxide. DNA damage and mutagenesis in the development of thyroid tu-mors. Nat Clin Pract Endocrinol Metab 2007;3:713-20. https://doi.org/10.1038/ncpendmet0621
  3. Griendling KK, FitzGerald GA. Oxidative stress and cardiovascular injury: part I. basic mechanisms and in vivo monitoring of ROS. Circulation 2003;108:1912-6. https://doi.org/10.1161/01.CIR.0000093660.86242.BB
  4. Sorescu D, Weiss D, Lassegue B, et al. Superoxide production and ex-pression of nox family proteins in human atherosclerosis. Circulation 2002;105:1429-35. https://doi.org/10.1161/01.CIR.0000012917.74432.66
  5. Brasen JH, Leppanen O, Inkala M, et al. Extracellular superoxide dismutase accelerates endothelial recovery and inhibits in-stent restenosis in stented atherosclerotic Watanabe heritable hyperlipidemic rabbit aorta. J Am Coll Cardiol 2007;50:2249-53. https://doi.org/10.1016/j.jacc.2007.08.038
  6. Powis G, Briehl M, Oblong J. Redox signaling and the control of cell growth and death. Pharmacol Ther 1995;68:149-73. https://doi.org/10.1016/0163-7258(95)02004-7
  7. Kang SW, Chae HZ, Seo MS, Kim K, Baines IC, Rhee SG. Mammalian peroxiredoxin isoforms can reduce hydrogen peroxide generated in response to growth factors and tumor necrosis factor-alpha. J Biol Chem 1998;273:6297-302. https://doi.org/10.1074/jbc.273.11.6297
  8. Nonn L, Williams RR, Erickson RP, Powis G. The absence of mitochondrial thioredoxin 2 causes massive apoptosis, exencephaly, and early embryonic lethality in homozygous mice. Mol Cell Biol 2003;23: 916-22. https://doi.org/10.1128/MCB.23.3.916-922.2003
  9. Asahara T, Murohara T, Sullivan A, et al. Isolation of putative progenitor endothelial cells for angiogenesis. Science 1997;275:964-7. https://doi.org/10.1126/science.275.5302.964
  10. Masuda H, Kalka C, Asahara T. Endothelial progenitor cells for rege-neration. Hum Cell 2000;13:153-60.
  11. Shioji K, Nakamura H, Masutani H, Yodoi J. Redox regulation by th-ioredoxin in cardiovascular diseases. Antioxid Redox Signal 2003;5: 795-802. https://doi.org/10.1089/152308603770380106
  12. Haendeler J, Tischler V, Hoffmann J, Zeiher AM, Dimmeler S. Low doses of reactive oxygen species protect endothelial cells from apoptosis by increasing thioredoxin-1 expression. FEBS Lett 2004;577:427-33. https://doi.org/10.1016/j.febslet.2004.10.041
  13. Kalka C, Masuda H, Takahashi T, et al. Transplantation of ex vivo expanded endothelial progenitor cells for therapeutic neovascularization. Proc Natl Acad Sci U S A 2000;97:3422-7. https://doi.org/10.1073/pnas.97.7.3422
  14. O'Donnell J, Mille-Baker B, Laffan M. Human umbilical-vein endothelial cells differ from other endothelial cells in failing to express ABO blood group antigens. J Vasc Res 2000;37:540-7. https://doi.org/10.1159/000054087
  15. Gershoni JM, Palade GE. Electrophoretic transfer of proteins from sodium docedcyl sulfate-polyacrylamide gels to a positively charged mem-brane filter. Anal Biochem 1982;124:396-405. https://doi.org/10.1016/0003-2697(82)90056-2
  16. Vane JR, Anggard EE, Botting RM. Regulatory functions of the vascular endothelium. N Engl J Med 1990;323:27-36. https://doi.org/10.1056/NEJM199007053230106
  17. Heitzer T, Schlinzig T, Krohn K, Meinertz T, Munzel T. Endothelial dys-function, oxidative stress, and risk of cardiovascular events inpatients with coronary artery disease. Circulation 2001;104:2673-8. https://doi.org/10.1161/hc4601.099485
  18. Fridlyand LE, Philipson LH. Oxidative reactive species in cell injury: mechanisms in diabetes mellitus and therapeutic approaches. Ann N Y Acad Sci 2005;1066:136-51. https://doi.org/10.1196/annals.1363.019
  19. Cho YS, Choi JH, Zhang SY, et al. Relationship of polymorphisms in the oxidative stress related genes-paraoxonase and p22phox to variant angina and coronary artery stenosis in Korean. Korean Circ J 2003; 33:104-12. https://doi.org/10.4070/kcj.2003.33.2.104
  20. Kim KS, Han HS, Lee YS, et al. Plasma thioredoxin level and its correlation to myocardial damage in patients with acute myocardial infarction who underwent successful primary angioplasty. Korean Circ J 2006;36:39-45. https://doi.org/10.4070/kcj.2006.36.1.39
  21. Ide T, Tsutsui H, Kniganwa S, et al. Mitochondrial electron transport complex I is a potential source of oxygen free radicals in the failing myo-cardium. Circ Res 1999;85:357-63. https://doi.org/10.1161/01.RES.85.4.357
  22. Powis G, Montfort WR. Properties and biological activities of thioredoxins. Annu Rev Pharmacol Toxicol 2001;41:261-95. https://doi.org/10.1146/annurev.pharmtox.41.1.261
  23. Becker K, Gromer S, Schirmer RH, Muller S. Thioredoxin reductase as a pathophysiological factor and drug target. Eur J Biochem 2000; 267:6118-25. https://doi.org/10.1046/j.1432-1327.2000.01703.x
  24. Okuda M, Inoue N, Azumi H, et al. Expression of glutaredoxin in human coronary arteries: its potential role in antioxidant protection against atherosclerosis. Arterioscler Thromb Vasc Biol 2001;21: 1483-7. https://doi.org/10.1161/hq0901.095550
  25. Haendeler J, Hoffmann J, Zeiher AM, Dimmeler S. Antioxidant effects of statins via S-nitrosylation and activation of thioredoxin in endothelial cells: a novel vasculoprotective function of statins. Circulation 2004;110:856-61. https://doi.org/10.1161/01.CIR.0000138743.09012.93
  26. Nishiyama A, Matsui M, Iwata S, et al. Identification of thioredoxin-binding protein-2/vitamin D(3) upregulated protein 1 as a negative re-gulator of thioredoxin function and expression. J Biol Chem 1999; 274:21645-50. https://doi.org/10.1074/jbc.274.31.21645
  27. Yoshioka J, Schulze PC, Cupesi M, et al. Thioredoxin-interacting protein controls cardiac hypertrophy through regulation of thioredoxin activity. Circulation 2004;109:2581-6. https://doi.org/10.1161/01.CIR.0000129771.32215.44
  28. World CJ, Yamawaki H, Berk BC. Thioredoxin in the cardiovascular system. J Mol Med 2006;84:997-1003. https://doi.org/10.1007/s00109-006-0109-6
  29. Bleeke T, Zhang H, Madamanchi N, Patterson C, Faber JE. Catecholoamine-induced vascular wall growth is dependent on generation of reactive oxygen species. Circ Res 2004;94:37-45. https://doi.org/10.1161/01.RES.0000109412.80157.7D
  30. Divakaran V, Mann DL. The emerging role of microRNAs in cardiac remodeling and heart failure. Circ Res 2008;103:1072-83. https://doi.org/10.1161/CIRCRESAHA.108.183087

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