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The age-related changes in DNA binding activity of AP-1, NF-κB, and OCT-1 transcription factors in lymphocytes from rats

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Abstract

The effect of aging on the induction of the ubiquitous transcription factors AP-1, NF-κB, and OCT-1 by concanavalin A (conA) was studied in nuclear extracts from spleen lymphocytes isolated from young (6 mo) and old (24 mo) male Fischer 344 rats. The induction of AP-1, NF-κB, and OCt-1 DNA binding activities were significantly lower (35 to 60%) in nuclear extracts from spleen lymphocytes isolated from old rats compared to nuclear extracts from spleen lymphocytes isolated from young rats. Because the transcription factor AP-1 consists of heterodimers of Fos and Jun oncoproteins, the induction of c-fos and c-jun expression (mRNA levels) by conA stimulated lymphocytes was measured using northern blot analysis. ConA induction of c-fos mRNA but not c-jun mRNA decreased approximately 70% with age. Therefore, the age-related decrease in the induction of AP-1 transcription factor appears to arise from alterations in c-fos expression.

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References

  1. Ullman, K. S., J. P. Northrop, C. L. Verweij, and G. R. Crabtree, Transmission of signals from the T lymphocyte antigen receptor to the genes responsible for cell proliferation and immune function: The missing link. Annu. Rev. Immunol., 8:421–452, 990.

  2. Johnson, P.F. and S.L. McKnight, Eukaryotic transcriptional regulatory protein. Annu. Rev. Biochem., 58:799–839, 1989.

    Article  PubMed  CAS  Google Scholar 

  3. McKnight, S. and R. Tijan, Transcriptional selectivity of viral genes in mammalian cells. Cell., 46: 795–802, 1986.

    Article  PubMed  CAS  Google Scholar 

  4. Baeuerle, P.A. and D. Baltimore, The physiology of NF-kB transcription factor. In: Hormonal Control Regulation of Gene Transcription. P. Cohen and J.G. Foulkes, (eds.) Elsevier Science Publishers, New York. 423–446.

  5. Angel, P., M. Imagawa, R. Chiu, B. Stein, R.J. Imbra, C. Jonat, and M. Karin, Porbol ester-inducible genes contain a common cis element recognized by a TPA-modulated transacting factor. Cell, 49:729–735, 1987.

    Article  PubMed  CAS  Google Scholar 

  6. Fletcher, C., Heintz, N., and R.G. Roeder, Purification and characterization of OTF-1, a transcription regulating cell cycle expression of a human histone H2b gene. Cell, 51:773–781, 1987.

    Article  PubMed  CAS  Google Scholar 

  7. Kroeger, P.E., Sarge, K.D., and R.I. Morimoto, Mouse heat shock transcription factors 1 and 2 prefer a trimeric binding site but interact differently with the HSP70 heat shock element. Mol. Cell. Biol. 13: 3370–3383, 1993.

    PubMed  CAS  Google Scholar 

  8. Lee, W., Mitchell, P. and R. Tjian, Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements. Cell., 49:741–752, 1978.

    Article  Google Scholar 

  9. Curran, T. and B.R. Franza, Fos and Jun: The AP-1 connection. Cell, 55:395–399, 1988.

    Article  PubMed  CAS  Google Scholar 

  10. Cohen, D.R., P.C. Ferreira, R. Gentz, and B.R. Franza, The product of a fos-related gene, fra-1, binds cooperatively to the AP-1 site with jun: Transcription factor AP-1 is composed of multiple protein complexes. Genes Dev., 3:173–178, 1989.

    PubMed  CAS  Google Scholar 

  11. Chiu, R., Boyle, W.J., Meek, J., Smeal, T., Hunter, T., and M. Karin, The c-fos protein interacts with c-jun/AP-1 to stimulate transcription of AP-1 responsive genes. Cell. 54:541–552, 1988.

    Article  PubMed  CAS  Google Scholar 

  12. Landshulz, W.H., Johnson, P.F., and S.L. McKnight, The Leucine Zipper: A hypothetical structure common to a new class of DNA binding proteins. Science, 240:1759–1764, 1988.

    Google Scholar 

  13. Sen, R. and D. Baltimore, Inducibility of kappa immunoglobulin enhancer-binding protein NF-kappa B by a posttranslational mechanism. Cell, 47:921–928, 1988.

    Article  Google Scholar 

  14. Baeuerle, P.A. and D. Baltimore, Activation of DNA-binding activity in an apparentlycytoplasmic precursor of the NF-kappa B transcription factor. Cell, 53:211–217, 1988.

    Article  PubMed  CAS  Google Scholar 

  15. Ghosh, S. and D. Baltimore, Activation if vitro of NF-kappa B by phosphorylation of its inhibitor I kappa B. Nature, 344:678–682, 1990.

    Article  PubMed  CAS  Google Scholar 

  16. Ghosh, S., Gifford, A.M., Riviere, L.R. and D. Baltimore, Cloning of p50 DNA binding subunit of NF-KB: Homology to rel and dorsal. Cell, 62:1019–1029, 1990.

    Article  PubMed  CAS  Google Scholar 

  17. Schreck, R., Rieber, P., and P.A. Baeuerle, Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kB transcription factor and HIV-1. EMBO J. 1:2247–2252, 1991.

    Google Scholar 

  18. Staal, F.J., M. Roederer, and L.A. Herzenberg, Intracellular thiols regulates activation of nuclear factor kB and transcription of human immunodeficiency virus. Proc. Natl. Acad. Sci. USA, 87:9943–9948, 1990.

    PubMed  CAS  Google Scholar 

  19. Harvey, R.P., Robins, A.J., and J.R., Wells, Independently evolving chicken histone H2B genes: Identification of a ubiquitous H2B-specific 5′ element. Nucleic Acid Res. 10:7851–7855, 1982.

    PubMed  CAS  Google Scholar 

  20. Goldsmith, MA. and A. Weiss, Early signal transduction by the antigen receptor without commitment to T cell activation. Science, 240:1029–1031, 1988.

    PubMed  CAS  Google Scholar 

  21. Maruyama, M., Shibuya, H, Hara, H., Hatadeyama, S, Seiki, M, Fugita, T., and Taniguchi, T., Evidence for aberrant activation of IL-2 autocrine loop by HTLV-1 encoded p40x and T3/Ti complex triggering. Cell, 48: 343–352, 1987.

    Article  PubMed  CAS  Google Scholar 

  22. Voss, J.W., L. Wilson, and M.G., Rosenfeld, POU-domain proteins Pit-1 and Oct-1 interact to form a heteromeric complex and can cooperate to induce expression of the prolactin promoter. Genes Dev., 5: 1309–1320, 1991.

    PubMed  CAS  Google Scholar 

  23. O’Neil, E.A., and T.J. Kelly, Purification and characterization of nuclear factor III (origin recognition protein C), a sequence-specific DNA binding protein required for efficient initiation of adenovirus DNA replication. J. Biol. Chem., 263:931–937, 1988.

    Google Scholar 

  24. Staudt, L.M., Clerc, R.G., Singh, H., LeBowitz, J.H., Sharp, P.A., and D. Baltimore, Cloning of a lymphoid specific cDNA encoding a protein binding the regulatory octamer DNA motif. Science, 241:577–580, 1988.

    PubMed  CAS  Google Scholar 

  25. Coleman, G.L., Barthold, S.W., Osbaldiston, G.W., Foster, S.J., and A. M. Jonas, Pathological changes during aging in barrier-reared Fischer 344 male rats. J. Gerontol. 32, 258–267, 1977.

    PubMed  CAS  Google Scholar 

  26. Pahlavani, M.A., D. Harris and A. Richardson, The age-related decline in the induction of IL-2 transcription is correlated to changes in the transcription factor NFAT. Cell. Immunol., 165:84–91, 1995.

    Article  PubMed  CAS  Google Scholar 

  27. Pahlavani, M. Aand M.D. Harris, Effect of dehydroepiandrosterone on mitogen-induced lymphocyte proliferation and cytokine production in young and old F344 rats. Immunol. Lett., 47:9–14, 1995.

    Article  PubMed  CAS  Google Scholar 

  28. Novak, T.G., P.M. White, and E.V. Rosenberg, Regulatory anatomy of the murine interleukin-2 gene. Nucleic Acid Res., 18:4523–4534, 1990.

    PubMed  CAS  Google Scholar 

  29. Jamieson, C., A. McCaffrey, A. Roa, and R. Sen, Physiologic activation of T cells via the T cell receptor induces NF-κKB. J. Immunol., 147:416–423, 1991.

    PubMed  CAS  Google Scholar 

  30. Chomczynski, P. and N. Sacchi, Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem Anal. Biochem., 162: 157–165, 1987.

    Google Scholar 

  31. Albright, J.W., J.C. Pflucker, and J.F. Albright, Transcriptional control of IL-2 and IL-4 in T cells of young and old mice. Cell. Immunol., 164:170–175, 1995.

    Article  PubMed  CAS  Google Scholar 

  32. Prasad, A.V., W.H. Pilcher, and S.A. Joseph, Nuclear factor-kB in rat brain: enhanced DNA-binding activity following convulsant-induced seizures. Neuroscience Lett., 170:145–148, 1994.

    Article  CAS  Google Scholar 

  33. Nagelkerken, L., Hertogh-Huijbregts, A., Dobber, R., and A. Draeger, Age-related changes in lymphokine production related to a decreased number of CD45RBhiCD4+ cells. Eur. J. Immunol., 21:273–281, 1991.

    PubMed  CAS  Google Scholar 

  34. Hobbs, M.V., Weigle, W.O., Noonan, D.J., Torbett, B.E., McEvilly, R.J., Koch, R.J., Cardenas, G.J., and Ernst, D.N. Patterns of Cytokine Gene Expression by CD4+ T Cells from Young and Old Mice. J. Immunol., 150:3602–3614, 1993.

    PubMed  CAS  Google Scholar 

  35. Sikora, E., B. Kaminska, E. Radziszewska, and L. Kaczmarek, Loss of transcription factor AP-1 DNA binding activity during lymphocyte aging in vivo. FEBS Lett., 312:179–186, 1992.

    Article  PubMed  CAS  Google Scholar 

  36. Whisler, R., Beiqing, L., L.C. Wu, and M. Chen, Reduced activation of transcription factor AP-1 among peripheral blood T cells from elderly humans after PHA stimulation: Restorative effect of phorbol diesters. Cell. Immunol., 152:96–109, 1993.

    Article  PubMed  CAS  Google Scholar 

  37. Riabowol, K., J. Schiff, and M.Z. Gilman, Transcription factor AP-1 activity is required for inhibition of DNA synthesis and is lost during cellular aging. Proc. Natl. Acad. Sci. USA, 89:157–161, 1992.

    PubMed  CAS  Google Scholar 

  38. Trebilcock, G.U., and U. Ponnappan, Failure to degrade IkB-a in senescent T cells accounts for lowered induction of NF-κB. The 9th Internat. Cong. of Immunol., Page 183 (Abstract #4123).

  39. Song, L., J. M. Stephens, S. Kittur, G. D. Collins, J. E. Nagel, P. H. Pekala, and W. H. Adler, Expression of c-fos, c-jun, and jun B in peripheral blood lymphocytes from young and elderly adults. Mech. Ageing Dev., 65:149–156, 1992.

    Article  PubMed  CAS  Google Scholar 

  40. Seshadri, T. and J. Campisi, Repression of c-fos transcription and an altered genetic program in senescent human fibroblasts. Science 247:205–208, 1990.

    PubMed  CAS  Google Scholar 

  41. Takahashi, R., H. Schunkert, S. Isoyama, J. Y. Wei, B. Nadal-Ginard, W. Grossman, and S. Izumo, Age-related differences in the expression of protooconogene and contractile protein genes in response to pressure overload in the rat myocardium. J. Clin. Invest., 89:939–946, 1992.

    Article  PubMed  CAS  Google Scholar 

  42. Robbins, P.D., Horowitz, J.M., and R.C. Mulligan, Negative regulation of human c-f fos expression by the retinoblastoma gene product. Nature, 346:669–671, 1990.

    Article  Google Scholar 

  43. Kannan, P., Role of Transcription Factors in Ras Signal Transduction Pathway. The Cancer Bull., 47: 152–157, 1995.

    Google Scholar 

  44. Jackson, D.I., W. Verbi, A.I., Lazarovitis, and M.J. Crumpton, T lymphocyte Activation: The Role of Tyrosine Phosphorylation. Molecular Mechanisms ofthe Immune Response. In: Cancer Survey, Imperial Cancer Res, Fund., 22: 97–110, 1995.

    CAS  Google Scholar 

  45. Su, B, E. Jacinto, M. Hibi, T. Kallunki, M. Karin, and Y. Neriah, JNK is involved in signal integration during costimulation of T lymphocytes. Cell, 77:727–736, 1994.

    Article  PubMed  Google Scholar 

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  1. Geriatric Research, Education and Clinical Center, Audie L. Murphy Memorial Veterans Hospital, and Department of Physiology, University of Texas Health Science Center, San Antonio, Texas, 78284

    Mohammad A. Pahlavani & Melissa D. Harris

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  1. Mohammad A. Pahlavani
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Pahlavani, M.A., Harris, M.D. The age-related changes in DNA binding activity of AP-1, NF-κB, and OCT-1 transcription factors in lymphocytes from rats. AGE 19, 45–54 (1996). https://doi.org/10.1007/BF02434070

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