Skip to main content


You are viewing the new article page. Let us know what you think. Return to old version

Enhanced expression of selenocysteine lyase in acute glomerulonephritis and its regulation by AP-1


Acute glomerulonephritis can lead to chronic glomerulonephritis or resolve without permanent damage to the kidneys. Differential gene expression was studied in a model of acute and chronic glomerulonephritis to identify factors influencing the course of glomerulonephritis towards healing or chronification. One of the differentially expressed genes was identified as SCL, encoding selenocysteine lyase. Its expression was higher in acute glomerulonephritis and lower in chronic glomerulonephritis. The transcriptional regulation of SCL was studied in vitro in rat mesangial cells (MC). SCL RNA expression increased eight-fold compared to the baseline after stimulation with interleukin-1β (IL-1β) for three hours. Luciferase expression and gel shift experiments revealed an enhancer element between bp −152 and −298 of the SCL 5’-regulatory region, with protein binding to an AP-1 binding site that may be involved in the regulation of SCL-RNA in vivo in an endogenous feedback mechanism to the inflammatory reaction in acute glomerulonephritis, leading to resolution of this disease.



anti-rat thymocyte serum


end-stage renal disease






mesangial cells


periodic acid-Schiff


polymerase chain reaction


selenocysteine lyase


  1. 1.

    Jefferson, J.A. and Johnson, R.J. Experimental mesangial proliferative glomerulonephritis (the anti-Thy-1.1 model). J. Nephrol. 12 (1999) 297–307.

  2. 2.

    Stahl, R.A.K., Thaiss, F., Wenzel, U., Schoeppe, W. and Helmchen, U. A rat model of progressive chronic glomerular sclerosis: the role of thromboxane inhibition. J. Am. Soc. Nephrol. 2 (1992) 1568–1577.

  3. 3.

    Harendza, S., Schneider, A., Helmchen, U. and Stahl, R.A.K. Extracellular matrix deposition and cell proliferation in a model of chronic glomerulonephritis in the rat. Nephrol. Dial. Transplant. 14 (1999) 2873–2879.

  4. 4.

    Jocks, T., Zahner, G., Freudenberg, J., Wolf, G., Thaiss, F., Helmchen, U. and Stahl, R.A.K. Prostaglandin E1 reduces the glomerular mRNA expression of monocyte-chemoattractant protein 1 in anti-thymocyte antibody-induced glomerular injury. J. Am. Soc. Nephrol. 7 (1996) 897–905.

  5. 5.

    Oberle, G.P., Niemeyer, J., Thaiss, F., Schoeppe, W. and Stahl, R.A.K. Increased oxygen radical and eicosanoid formation in immune-mediated mesangial cell injury. Kidney Int. 42 (1992) 69–74.

  6. 6.

    Stahl, R.A.K., Thaiss, F., Disser, M., Helmchen, U., Hora, K. and Schlöndorff, D. Increased expression of monocyte chemoattractant protein-1 in anti-thymocyte antibody-induced glomerulonephritis. Kidney Int. 44 (1993) 1036–1047.

  7. 7.

    Schneider, A., Panzer, U., Zahner, G., Wenzel, U., Wolf, G., Thaiss, F., Helmchen, U. and Stahl, R.A.K. Monocyte-chemoattractant protein-1 mediates collagen deposition in experimental glomerulonephritis by transforming growth factor-beta. Kidney Int. 56 (1999) 135–144.

  8. 8.

    Esaki, N., Nakamura, T., Tanaka, H. and Soda, K. Selenocysteine lyase, a novel enzyme that specifically acts on selenocysteine. J. Biol. Chem. 157 (1982) 4386–4391.

  9. 9.

    Arnér, E.S.J. and Holmgren, A. Physiological functions of thioredoxin and thioredoxin reductase. Eur. J. Biochem. 267 (2000) 6102–6109.

  10. 10.

    Brigelius-Flohé, R. Tissue-specific functions of individual glutathione peroxidases. Free Radic. Biol. Med. 27 (1999) 951–965.

  11. 11.

    Mosley, K., Waddington, S.N., Ebrahim, H., Cook, C. and Cattell, V. Inducible nitric oxide synthase induction in Thy-1 glomerulonephritis is complement and reactive oxygen species dependent. Exp. Nephrol. 7 (1999) 26–34.

  12. 12.

    Stahl, R.A.K., Thaiss, F., Oberle, G., Brecht, H.M., Schoeppe, W., Wenzel, U. and Helmchen, U.M. The platelet activating factor receptor antagonist WEB 2170 improves glomerular hemodynamics and morphology in a proliferative model of mesangial injury. J. Am. Soc. Nephrol. 2 (1991) 37–44.

  13. 13.

    Burlington, H. and Cronkite, E.P. Characteristics of cell cultures derived from renal glomeruli. Proc. Soc. Exp. Bio Med. 142 (1973) 143–149.

  14. 14.

    Harper, P.A., Robinson, J.M., Hoover, R.L., Wright, T.C. and Karnovsky, M. J. Improved methods for culturing rat glomerular cells. Kidney Int. 26 (1984) 875–880.

  15. 15.

    Chirgwin, J.M., Przybyla, A.E., MacDonald, R.J. and Rutter, W.J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry 18 (1979) 5294–5299.

  16. 16.

    Boussif, O., Lezoualc’h, F., Zanta, M.A., Mergny, M.D., Scherman, D., Demeneix, B. and Behr, J.P. A versatile vector for gene and oligonucleotide transfer into cells in culture and in vivo: polyethylenimime. Proc. Natl. Acad. Sci. USA 92 (1995) 7297–7301.

  17. 17.

    Brasier, A.R., Tate, J.E. and Habener, J.F. Optimized use of the firefly luciferase assay as a reporter gene in mammalian cell lines. BioTechniques 7 (1989) 1116–1122.

  18. 18.

    Rosenthal, N. Identification of regulatory elements of cloned genes with functional assays. Methods Enzymol. 152 (1987) 704–720.

  19. 19.

    Dignam, J.D., Lebovitz, R.M. and Roeder, R.G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 11 (1983) 1475–1489.

  20. 20.

    Wallenstein, S., Zucker, C.L. and Fleiss, J.L. Some statistical methods useful in circulation research. Circ. Res. 47 (1980) 1–9

  21. 21.

    Daher, R. and Van Lente, F. Characterization of selenocysteine lyase in human tissues and its relationship to tissue selenium concentrations. J. Trace Elem. Electrolytes Health Dis. 6 (1992) 189–194

  22. 22.

    Tesch, G.H., Yang, N., Yu, H., Lan, H.Y., Foti, R., Chadban, S.J, Atkins, R.C. and Nikolic-Paterson, D.J. Intrinsic renal cells are the major source of interleukin-1 beta synthesis in normal and diseased rat kidney. Nephrol. Dial. Transplant. 12 (1997) 1109–1115.

  23. 23.

    Gaertner, S.A., Janssen, U., Ostendorf, T., Koch, K.-M., Floege, J. and Gwinner, W. Glomerular oxidative and antioxidative systems in experimental mesangioproliferative glomerulonephritis. J. Am. Soc. Nephrol. 13 (2002) 2930–2937.

  24. 24.

    Wingender, E., Chen, X., Hehl, R., Karas, I., Liebich, I., Matys, V., Meinhardt, T., Pruss, M., Reuter, I. and Schacherer, F. TRANSFAC: an integrated system for gene expression regulation. Nucl. Acids Res. 28 (2000) 316–331.

  25. 25.

    Gimble, J.M., Flanagan, F.R., Recker, D. and Max, E.E. Identification and partial purification of a protein binding to the human immunoglobulin kappa enhancer κE2 site. Nucl. Acids Res. 11 (1988) 4967–4988

  26. 26.

    Kitamura, M., Ishikawa, Y., Moreno-Manzano, V., Xu, Q., Konta, T., Lucio-Cazana, J., Furusu, A. and Nakayama, K. Intervention by retinoic acid in oxidative stress-induced apoptosis. Nephrol. Dial. Transplant. 17 (2002) 84–87.

  27. 27.

    Karin, M., Liu, Z. and Zandi, E. AP-1 function and regulation. Curr. Op. Cell. Biol. 9 (1997) 240–246.

  28. 28.

    Panzer, U., Schneider, A., Guan, Y., Reinking, R., Zahner, G., Harendza, S., Wolf, G., Thaiss, F. and Stahl, R.A.K. Effects of different PPARgamma-agonists on MCP-1 expression and monocyte recruitment in experimental glomerulonephritis. Kidney Int. 62 (2002) 455–464.

Download references

Author information

Correspondence to Sigrid Harendza.

Rights and permissions

Reprints and Permissions

About this article

Key words

  • Selenocysteine lyase
  • Glomerulonephritis
  • Differential display
  • Inflammation
  • Mesangial cells
  • AP-1
  • Transcription