Skip to main content
SpringerLink
Log in

Enhanced binding of circulating SLE autoantibodies to catecholestrogen-copper-modified DNA

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease characterized by circulating and tissue fixed autoantibodies reactive with self-antigens, including nucleic acid and other nuclear components. The pathways by which these autoantibodies act as a pathogenic factor remain elusive. Present study has investigated the role of estrogens in SLE etiopathogenesis. Estrogen-modified DNA [4-OHE2-Cu(II)-DNA] showed single- and double-strand breaks, hyperchromicity, decrease in Tm, and modification of bases. The 4-OHE2-Cu(II)-DNA exhibited increased binding with naturally occurring anti-DNA autoantibodies as compared to the unmodified native form (P < 0.001) as assessed by ELISA, quantitative precipitin titration, and gel retardation assay. The relative affinity of anti-DNA antibodies for modified and native DNA was in the order of 2.1 × 10−7 M and 1.3 × 10−6 M, respectively. The data suggested that DNA modified with 4-OHE2 and Cu(II) may be one of the factors for the induction of circulating anti-DNA autoantibodies in SLE.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Cutolo M, Capellino S, Sulli A, Serioli B, Secchi ME, Villaggio B et al (2006) Estrogens and autoimmune diseases. Ann N Y Acad Sci 1089:538–547. doi:10.1196/annals.1386.043

    Article  PubMed  CAS  Google Scholar 

  2. Gomez CR, Plackett TP, Kovacs EJ (2007) Aging and estrogen: modulation of inflammatory responses after injury. Exp Gerontol 42:451–456. doi:10.1016/j.exger.2006.11.013

    Article  PubMed  CAS  Google Scholar 

  3. Straub RH (2007) The Complex Role of Estrogens in Inflammation. Endocr Rev 28:521–574. doi:10.1210/er.2007-0001

    Article  PubMed  CAS  Google Scholar 

  4. Cohen-Solal JF, Jeganathan V, Grimaldi CM, Peeva E, Diamond B (2006) Sex hormones and SLE: influencing the fate of autoreactive B cells. Curr Top Microbiol Immunol 305:67–88

    Article  PubMed  CAS  Google Scholar 

  5. Mc Murray RW (2001) Sex hormones in the pathogenesis of systemic lupus erythematosus. Front Biosci 6:E193–E206. doi:10.2741/McMurray

    Article  CAS  Google Scholar 

  6. Jacobson DL, Gange SJ, Rose NR, Graham NMH (1997) Epidemiology and estimated population burden of selected autoimmune disease in the United States. Clin Immunol Immunopathol 84:223–243. doi:10.1006/clin.1997.4412

    Article  PubMed  CAS  Google Scholar 

  7. Grossman C, Roselle G, Mendenhall C (1991) Sex steroid regulation of autoimmunity. J Steroid Biochem Mol Biol 40:649–659. doi:10.1016/0960-0760(91)90287-F

    Article  PubMed  CAS  Google Scholar 

  8. Weidler C, Harle P, Schedel J, Schmidt M, Scholmerich J, Straub RH (2004) Patients with rheumatoid arthritis and systemic lupus erythematosus have increased renal excretion of mitogenic estrogen in relation to endogenous antiestrogens. J Rheumatol 31:489–494

    PubMed  CAS  Google Scholar 

  9. Lahita RG, Bradlow HL, Kunal HG, Fishman J (1979) Alteration of estrogen metabolism in systemic lupus erythematosus. Arthritis Rheum 22:1195–1198. doi:10.1002/art.1780221106

    Article  PubMed  CAS  Google Scholar 

  10. Castagnetta L, Carruba G, Granata OM, Stefano R, Miele M, Schmidt M et al (2003) Increased estrogen formation and estrogen to androgen ratio in the SF of patients with rheumatoid arthritis. J Rheumatol 30:2597–2605

    PubMed  CAS  Google Scholar 

  11. Lahita RG (1996) The connective tissue diseases and the overall influence of gender. Int J Fertil Menopausal Stud 41:156–160

    PubMed  CAS  Google Scholar 

  12. Bremner I, Beattie JH (1995) Copper and zinc metabolism in health and disease: speciation and interactions. Proc Nutr Soc 54:489–499. doi:10.1079/PNS19950017

    Article  PubMed  CAS  Google Scholar 

  13. Haschke F, Ziegler EE, Edwards BB, Fomon SJ (1986) Effect of iron fortification of infant formula on trace mineral absorption. J Pediatr Gastroenterol Nutr 5:768–773. doi:10.1097/00005176-198609000-00018

    Article  PubMed  CAS  Google Scholar 

  14. Harris ED, Percival SS (1991) A role for ascorbic acid in copper transport. Am J Clin Nutr 54:1193S–1197S

    PubMed  CAS  Google Scholar 

  15. Saltman PD, Strause LG (1993) The role of trace minerals in osteoporosis. J Am Coll Nutr 12:384–389

    PubMed  CAS  Google Scholar 

  16. Cashman KD, Baker A, Ginty F, Strain JJ, Bonham MP, O’Connor JM et al (2001) No effect of copper supplementation on biochemical markers of bone metabolism in healthy young adult females despite apparently improved copper status. Eur J Clin Nutr 55:525–553. doi:10.1038/sj.ejcn.1601177

    Article  PubMed  CAS  Google Scholar 

  17. Manson JJ, Isenberg DA (2003) The pathogenesis of systemic lupus erythematosus. Neth J Med 61:343–346

    PubMed  CAS  Google Scholar 

  18. Cameron JJ (1999) Clinical manifestations of lupus nephritis. In: Lewis EJ, Schwartz MM, Korbet SM (eds) Lupus nephritis. Oxford University Press, Oxford, pp 159–184

    Google Scholar 

  19. Waldman M, Madaio MP (2005) Pathogenic autoantibodies in lupus nephritis. Lupus 14:19–24. doi:10.1191/0961203305lu2054oa

    Article  PubMed  CAS  Google Scholar 

  20. Khan WA, Moinuddin (2006) Binding Characteristics of SLE anti-DNA autoantibodies to Catecholestrogen-modified DNA. Scand J Immunol 64:677–683. doi:10.1111/j.1365-3083.2006.01855.x

    Article  PubMed  CAS  Google Scholar 

  21. Khan WA, Alam K, Moinuddin (2007) Catechol-estrogen modified DNA: A better antigen for cancer autoantibody. Arch Biochem Biophys 465:293–300. doi:10.1016/j.abb.2007.06.006

    Article  PubMed  CAS  Google Scholar 

  22. Al Arfaj AS, Chawdhary AR, Khalil N, Ali R (2007) Immunogenicity of singlet oxygen modified human DNA: implication for anti-DNA antibodies in systemic lupus erythematosus. Clin Immunol 124:83–89. doi:10.1016/j.clim.2007.03.548

    Article  PubMed  CAS  Google Scholar 

  23. Mansoor F, Ali A, Ali R (2005) Binding of circulating SLE autoantibodies to oxygen free radical damaged chromatin. Autoimmunity 38:431–438. doi:10.1080/08916930500288596

    Article  PubMed  CAS  Google Scholar 

  24. Gark DK, Ali R, Moinuddin (2003) Hydroxyl modification of polyguanilic acid: role of modified guanine in circulating SLE anti-DNA autoantibodies. Immunol Invest 32:187–199. doi:10.1081/IMM-120022978

    Article  CAS  Google Scholar 

  25. Waris G, Alam K (2004) Immunogenicity of superoxide radical modified-DNA: studies on induced antibodies and SLE anti-DNA autoantibodies. Life Sci 75:2633–2642. doi:10.1016/j.lfs.2004.04.034

    Article  PubMed  CAS  Google Scholar 

  26. Habib S, Ali R, Moinuddin (2006) Peroxynitrite-modified DNA: a better antigen for systemic lupus erythematosus anti-DNA autoantibodies. Biotechnol Appl Biochem 43:65–70. doi:10.1042/BA20050156

    Article  PubMed  CAS  Google Scholar 

  27. Habib S, Ali R, Moinuddin (2005) Acquired antigenicity of DNA after modification with peroxynitrite. Int J Biol Macromol 35:221–225. doi:10.1016/j.ijbiomac.2005.02.005

    Article  PubMed  CAS  Google Scholar 

  28. Arnett FC, Edworthy TA, Bloch DA, Mcshaie DJ, Fries JF, Cooper NS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31:315–324. doi:10.1002/art.1780310302

    Article  PubMed  CAS  Google Scholar 

  29. Hasan R, Ali R (1990) Antibody recognition of common epitopes on Z-DNA and native DNA brominated under high salt. Biochem Int 20:1077–1088

    PubMed  CAS  Google Scholar 

  30. Ali R, Alam K (2002) Evaluation of antibodies against free radical modified DNA by ELISA. In: Armstrong D (ed) Oxidative stress biomarkers and antioxidants protocols. Human Press, New Jersey, pp 171–181

    Chapter  Google Scholar 

  31. Dixit K, Ali R (2001) Antigen binding characteristics of antibodies induced against nitric oxide modified plasmid DNA. Biochim Biophys Acta 1528:1–8

    PubMed  CAS  Google Scholar 

  32. Burton K (1956) A study of the conditions and mechanisms of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J 62:315–323

    PubMed  CAS  Google Scholar 

  33. Bradford MM (1976) A rapid and sensitive method for quantitation of micrograms quantity of protein utilizing the principle of protein dye binding. Anal Biochem 72:248–254. doi:10.1016/0003-2697(76)90527-3

    Article  PubMed  CAS  Google Scholar 

  34. Langmuir I (1918) The adsorption of gases on plane surface glass, mica and platinum. J Am Chem Soc 40:1361–1403. doi:10.1021/ja02242a004

    Article  CAS  Google Scholar 

  35. Jansson G (1985) Formation of antibodies to native DNA in rats after administration of native DNA treated with xanthine-xanthine oxidase system. Free Radic Res Commun 1:119–122. doi:10.3109/10715768509056544

    Article  PubMed  CAS  Google Scholar 

  36. Riemekasten G, Hahn BH (2005) Key autoantigens in SLE. Rheumatology 44:975–982. doi:10.1093/rheumatology/keh688

    Article  PubMed  CAS  Google Scholar 

  37. Mok CC, Lau CS (2003) Pathogenesis of systemic lupus erythematosus. J Clin Pathol 56:481–490. doi:10.1136/jcp. 56.7.481

    Article  PubMed  CAS  Google Scholar 

  38. Agarwal K, Sharma A, Taluder G (1989) Effects of copper on mammalian cell components. Chem Biol Interact 69:1–16. doi:10.1016/0009-2797(89)90094-X

    Article  PubMed  CAS  Google Scholar 

  39. Bryan SE, Vizard DL, Beary DA, Biche RA, Hardy KJ (1981) Partitioning of zinc and copper within sub-nuclear nucleoprotein particles. Nucleic Acids Res 9:5811–5823. doi:10.1093/nar/9.21.5811

    Article  PubMed  CAS  Google Scholar 

  40. Whitehouse MW (1976) Ambivalent role of copper in inflammatory disorders. Inflamm Res 6:201–206

    CAS  Google Scholar 

  41. Brewer GJ (2005) Anti-copper therapy against cancer and diseases of inflammation and fibrosis. Drug Discov Today 10:1103–1109. doi:10.1016/S1359-6446(05)03541-5

    Article  PubMed  CAS  Google Scholar 

  42. Zhu BT, Conney AH (1998) Functional role of estrogen metabolism in target cells: review and perspectives. Carcinogenesis 19:1–27. doi:10.1093/carcin/19.1.1

    Article  PubMed  Google Scholar 

  43. Cavalieri E, Frenkel K, Liehr JG, Rogan E, Roy D (2000) Estrogen as endogenous genotoxic agents—DNA adducts and mutation. J Natl Cancer Inst Monogr 27:75–93

    PubMed  CAS  Google Scholar 

  44. Cutolo M, Sulli A, Seriolo B, Accardo S, Masi AT (1995) Estrogens, the immune response and autoimmunity. Clin Exp Rheumatol 13:217–226

    PubMed  CAS  Google Scholar 

  45. Stollar BD (1989) Immunochemistry of DNA. Int Rev Immunol 5:1–22. doi:10.3109/08830188909086987

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors thank Prof. Rashid Ali for his continuous help and support. We are greatly thankful to him for providing lab facility and constructive discussions during this work.

Author information

Author notes

  1. Wahid Ali Khan

    Present address: Indian Spinal Injuries Centre, Sector-C, Vasant Kunj, New Delhi, 110070, India

Authors and Affiliations

  1. Department of Biochemistry, J. N. Medical College, A. M. U., Aligarh, 202002, India

    Wahid Ali Khan, Safia Habib, Wajid Ali Khan, Khursheed Alam &  Moinuddin

Authors
  1. Wahid Ali Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Safia Habib
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wajid Ali Khan
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Khursheed Alam
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Moinuddin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Moinuddin.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Khan, W.A., Habib, S., Khan, W.A. et al. Enhanced binding of circulating SLE autoantibodies to catecholestrogen-copper-modified DNA. Mol Cell Biochem 315, 143–150 (2008). https://doi.org/10.1007/s11010-008-9798-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11010-008-9798-1

Keywords

Search

Navigation