DOI QR코드

DOI QR Code

Inactive extracellular superoxide dismutase disrupts secretion and function of active extracellular superoxide dismutase

  • Jeon, Byeong-Wook (Laboratory of Dermato-Immunology, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea) ;
  • Kim, Byung-Hak (Laboratory of Dermato-Immunology, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea) ;
  • Lee, Yun-Sang (Laboratory of Dermato-Immunology, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea) ;
  • Kim, Sung-Sub (Youngin Frontier 5F) ;
  • Yoon, Jong-Bok (Department of Biochemistry and Translational Research Center for Protein Function Control, Yonsei University) ;
  • Kim, Tae-Yoon (Laboratory of Dermato-Immunology, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea)
  • Received : 2010.11.09
  • Accepted : 2010.11.22
  • Published : 2011.01.31

Abstract

Extracellular superoxide dismutase (EC-SOD) is an antioxidant enzyme that protects cells and tissues from extracellular damage by eliminating superoxide anion radicals produced during metabolism. Two different forms of EC-SOD exist, and their different enzyme activities are a result of different disulfide bond patterns. Although only two folding variants have been discovered so far, five folding variants are theoretically possible. Therefore, we constructed five different mutant EC-SOD expression vectors by substituting cysteine residues with serine residues and evaluated their expression levels and enzyme activities. The mutant EC-SODs were expressed at lower levels than that of wild-type EC-SOD, and all of the mutants exhibited inhibited extracellular secretion, except for C195S ECSOD. Finally, we demonstrated that co-expression of wild-type EC-SOD and any one of the mutant EC-SODs resulted in reduced secretion of wild-type EC-SOD. We speculate that mutant EC-SOD causes malfunctions in systems such as antioxidant systems and sensitizes tissues to ROS-mediated diseases.

Keywords

References

  1. Hruza, L. L. and Pentland, A. P. (1993) Mechanisms of UV-induced inflammation. J. Invest. Dermatol. 100, 35S-41S.
  2. Fattman, C. L., Schaefer, L. M. and Oury, T. D. (2003) Extracellular superoxide dismutase in biology and medicine. Free Radic. Biol. Med. 35, 236-256. https://doi.org/10.1016/S0891-5849(03)00275-2
  3. Oury, T. D., Chang, L. Y., Marklund, S. L., Day, B. J. and Crapo, J. D. (1994) Immunocytochemical localization of extracellular superoxide dismutase in human lung. Lab. Invest. 70, 889-898.
  4. Oury, T. D., Day, B. J. and Crapo, J. D. (1996) Extracellular superoxide dismutase in vessels and airways of humans and baboons. Free Radic. Biol. Med. 20, 957-965. https://doi.org/10.1016/0891-5849(95)02222-8
  5. Marklund, S. L. (1984) Extracellular superoxide dismutase in human tissues and human cell lines. J. Clin. Invest. 74, 1398-1403. https://doi.org/10.1172/JCI111550
  6. Marklund, S. L. (1982) Human copper-containing superoxide dismutase of high molecular weight. Proc. Natl. Acad. Sci. U.S.A. 79, 7634-7638. https://doi.org/10.1073/pnas.79.24.7634
  7. Olsen, D. A., Petersen, S. V., Oury, T. D., Valnickova, Z., Thøgersen, I. B., Kristensen, T., Bowler, R. P., Crapo, J. D. and Enghild, J. J. (2004) The intracellular proteolytic processing of extracellular superoxide dismutase (EC-SOD) is a two-step event. J. Biol. Chem. 279, 22152-22157. https://doi.org/10.1074/jbc.M401180200
  8. Tibell, L. A., Skärfstad, E. and Jonsson, B. H. (1996) Determination of the structural role of the N-terminal domain of human extracellular superoxide dismutase by use of protein fusions. Biochim. Biophys. Acta 1292, 47-52. https://doi.org/10.1016/0167-4838(95)00189-1
  9. Hjalmarsson, K., Marklund, S. L., Engstrom, A. and Edlund, T. (1987) Isolation and sequence of complementary DNA encoding human extracellular superoxide dismutase. Proc. Natl. Acad. Sci. U.S.A. 84, 6340-6344. https://doi.org/10.1073/pnas.84.18.6340
  10. Sandstrom, J., Carlsson, L., Marklund, S. L. and Edlund, T. (1992) The heparin-binding domain of extracellular superoxide dismutase C and formation of variants with reduced heparin affinity. J. Biol. Chem. 267, 18205-18209.
  11. Enghild, J. J., Thogersen, I. B., Oury, T. D., Valnickova, Z., Hojrup, P. and Crapo, J. D. (1999) The heparin-binding domain of extracellular superoxide dismutase is proteolytically processed intracellularly during biosynthesis. J. Biol. Chem. 274, 14818-14822. https://doi.org/10.1074/jbc.274.21.14818
  12. Petersen, S. V., Oury, T. D., Ostergaard, L., Valnickova, Z., Wegrzyn, J., Thogersen, I. B., Jacobsen, C., Bowler, R. P., Fattman, C. L., Crapo, J. D. and Enghild, J. J. (2004) Extracellular superoxide dismutase (EC-SOD) binds to type I collagen and protects against oxidative fragmentation. J. Biol. Chem. 279, 13705-13710. https://doi.org/10.1074/jbc.M310217200
  13. Petersen, S. V., Olsen, D. A., Kenney, J. M., Oury, T. D., Valnickova, Z., Thogersen, I. B., Crapo, J. D. and Enghild, J. J. (2005) The high concentration of $Arg213{\to}Gly$ extracellular superoxide dismutase (EC-SOD) in plasma is caused by a reduction of both heparin and collagen affinities. Biochem. J. 385, 427-432. https://doi.org/10.1042/BJ20041218
  14. Oury, T. D., Crapo, J. D., Valnickova, Z. and Enghild, J. J. (1996) Human extracellular superoxide dismutase is a tetramer composed of two disulphide-linked dimers: a simplified, high-yield purification of extracellular superoxide dismutase. Biochem. J. 317, 51-57. https://doi.org/10.1042/bj3170051
  15. Carlsson, L. M., Marklund, S. L. and Edlund, T. (1996) The rat extracellular superoxide dismutase dimer is converted to a tetramer by the exchange of a single amino acid. Proc. Natl. Acad. Sci. U.S.A. 93, 5219-5222. https://doi.org/10.1073/pnas.93.11.5219
  16. Antonyuk, S. V., Strange, R. W., Marklund, S. L. and Hasnain, S. S. (2009) The structure of human extracellular Copper-Zinc superoxide dismutase at 1.7 ${\AA}$ Resolution: Insights into Heparin and Collagen Binding. J. Mol. Biol. 388, 310-326. https://doi.org/10.1016/j.jmb.2009.03.026
  17. Ellgaard, L. and Ruddock, L. W. (2005) The human protein disulphide isomerase family: substrate interactions and functional properties. EMBO Rep. 6, 28-32. https://doi.org/10.1038/sj.embor.7400311
  18. Schmidt, B., Ho, L. and Hogg, P. J. (2006) Allosteric disulfide bonds. Biochemistry 45, 7429-7433. https://doi.org/10.1021/bi0603064
  19. Turano, C., Coppari, S., Altieri, F. and Ferraro, A. (2002) Proteins of the PDI family: Unpredicted non-ER locations and functions. J. Cell. Physiol. 193, 154-163. https://doi.org/10.1002/jcp.10172
  20. Chen, V. M., Ahamed, J., Versteeg, H. H., Berndt, M. C., Ruf, W. and Hogg, P. J. (2006) Evidence for activation of tissue factor by an allosteric disulfide bond. Biochemistry 45, 12020-12028. https://doi.org/10.1021/bi061271a
  21. Petersen, S. V., Oury, T. D., Valnickova, Z., Thogersen, I. B., Hojrup, P., Crapo, J. D. and Enghild, J. J. (2003) The dual nature of human extracellular superoxide dismutase: One sequence and two structures. Proc. Natl. Acad. Sci. U.S.A. 100, 13875-13880. https://doi.org/10.1073/pnas.2436143100
  22. Petersen, S. V., Due, A. V., Valnickova, Z., Oury, T. D., Crapo, J. D. and Enghild, J. J. (2004) The structure of rabbit extracellular superoxide dismutase differs from the human protein. Biochemistry 43, 14275-14281. https://doi.org/10.1021/bi048526+
  23. Getzoff, E. D., Tainer, J. A., Stempien, M. M., Bell, G. I. and Hallewell, R. A. (1989) Evolution of CuZn superoxide dismutase and the Greek key beta-barrel structural motif. Proteins 5, 322-336. https://doi.org/10.1002/prot.340050408
  24. Petersen, S. V., Kristensen, T., Petersen, J. S., Ramsgaard, L., Oury, T. D., Crapo, J. D., Nielsen, N. C. and Enghild, J. J. (2008) The folding of human active and inactive extracellular superoxide dismutases is an intracellular event. J. Biol. Chem. 283, 15031-15036. https://doi.org/10.1074/jbc.M801548200
  25. Petersen, S. V., Valnickova, Z., Oury, T. D., Crapo, J. D., Nielsen, N. C. and Enghild, J. J. (2007) The subunit composition of human extracellular superoxide dismutase (ECSOD) regulate enzymatic activity. BMC Biochem. 8, 19. https://doi.org/10.1186/1471-2091-8-19
  26. Lederkremer, G. Z. (2009) Glycoprotein folding, quality control and ER-associated degradation. Curr. Opin. Struct. Biol. 19, 515-523. https://doi.org/10.1016/j.sbi.2009.06.004
  27. Sakoh-Nakatogawa, M., Nishikawa, S. and Endo, T. (2009) Roles of protein-disulfide isomerase-mediated disulfide bond formation of yeast Mnl1p in endoplasmic reticulum-associated degradation. J. Biol. Chem. 284, 11815-11825. https://doi.org/10.1074/jbc.M900813200
  28. Due, A. V., Petersen, S. V., Valnickova, Z., Ostergaard, L., Oury, T. D., Crapo, J. D. and Enghild, J. J. (2006) Extracellular superoxide dismutase exists as an octamer. FEBS Lett. 580, 1485-1489. https://doi.org/10.1016/j.febslet.2006.01.081

Cited by

  1. IFNγ-mediated inhibition of cell proliferation through increased PKCδ-induced overexpression of EC-SOD vol.45, pp.11, 2012, https://doi.org/10.5483/BMBRep.2012.45.11.003
  2. Rational design of a secreted enzymatically inactive mutant of extracellular superoxide dismutase vol.17, pp.6, 2012, https://doi.org/10.1179/1351000212Y.0000000028
  3. J7, a methyl jasmonate derivative, enhances TRAIL-mediated apoptosis through up-regulation of reactive oxygen species generation in human hepatoma HepG2 cells vol.26, pp.1, 2012, https://doi.org/10.1016/j.tiv.2011.10.016
  4. Cloning and expression analysis ofDrosophilaextracellular Cu Zn superoxide dismutase vol.34, pp.6, 2014, https://doi.org/10.1042/BSR20140133