Cardiovascular Toxicology

, Volume 5, Issue 2, pp 183–201 | Cite as

NF-κB in cardiovascular disease

Diverse and specific effects of a “General” transcription factor?
  • W. Keith Jones
  • Maria Brown
  • Michael Wilhide
  • Suiwen He
  • Xiaoping Ren
Original Research

Abstract

The transcription factor NF-κB regulates a wide variety of biological effects in diverse cell types and organs, particularly stress and adaptive responses. Recently, it has become recognized that NF-κB and its upstream regulator tumor necrosis factor (TNF)-α regulate specific antithetical effects. For instance, in the heart, NF-κB has been found to be required for development of late preconditioning against myocardial infarction and yet is critically involved in mediating cell death after ischemia/reperfusion injury. There remains a bias that NF-κB is a “general” transcription factor that is activated by a plethora of stimuli, including neurohormonal, pathophysiological, and stress stimuli, and affects regulation of numerous downstream genes. The question has become, how can such a “general” transcription factor be critically involved in mediating specific effects? An emerging hypothesis is that NF-κB is part of a complicated signaling network or web, and that different combinatorial interactions between various activated signaling pathway components produce specific outcomes. This idea is supported by the large number of interactions discovered in the past 14 years between NF-κB and other signaling pathways at multiple levels. Notwithstanding the complexities of signal-induced activation of NF-κB, since it is a transcription factor, specific effects of NF-κB activation must be underlain by the activation and/or suppression of distinct subsets of NF-κB-dependent genes. At this level, selectivity is conferred by the expression of specific NF-κB subunits, their post translational modifications, and by combinatorial interactions between NF-κB and other transcription factors and co-activators that form specific enhanceosome complexes in association with particular promoters. These enhanceosome complexes represent another level of signaling integration whereby the activities of multiple upstream pathways converge to impress a distinct pattern of gene expression upon the NF-κB-dependent transcriptional network.

Understanding how the overall cellular signaling network translates NF-κB activation into the regulation of specific subsets of NF-κB-dependent genes will lead to a mechanistic understanding of how NF-κB mediates diverse and paradoxical biological effects. In addition to the experimental approaches that have been historically undertaken, modern proteomic, geonomic, and computational modeling approaches need to be applied in an integrated manner to achieve a workable understanding of NF-κB regulation and the NF-κB-dependent transcriptional network. Since NF-κB is activated in association with disease and contributes functionally to pathophysiology, understanding the detailed mechanisms by which the seemingly generalized activation of NF-κB results in specific effects will allow us to identify particular signaling modules, transcriptional co-factors, protein complexes, and the discrete sets of NF-κB-dependent genes involved in specific effects. Certain of these may prove to be even better therapeutic targets than NF-κB, allowing us to block the injurious effects while preserving the potentially beneficial effects of adaptive signaling in the heart.

Key Words

Transcriptional network NF-κB signaling gene regulation transgenic models ischemia mathematical modeling heart 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Baldwin, A.S. Jr. (1996). The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu. Rev Immunol 14:649–683.PubMedCrossRefGoogle Scholar
  2. 2.
    Jones W.K., Brown, M. Ren, X., He, S., and McGuinness, M. (2003). NF-kappa B as an integrator of diverse signaling pathways: the heart of myocardial signaling? Cardiovascular Toxicology 3(3):229–253.PubMedCrossRefGoogle Scholar
  3. 3.
    Valen G. (2004). Signal transduction through nuclear factor kappa B in ischemia-reperfusion and heart failure. Basic Res. Cardiol. 99(1):1–7.PubMedCrossRefGoogle Scholar
  4. 4.
    Kumar, A., Takada, Y., and Boriek, A.M. (2004). Nuclear factor-κB: its role in health and disease. J. Mol. Med. 82: 434–448.PubMedCrossRefGoogle Scholar
  5. 5.
    Grumont, R.J. and Gerondakis, S. (1989). Structure of a mammalian c-rel protein deduced from the nucleotide sequence of murine cDNA clones. Oncogene Res. 4(1): 1–8.PubMedGoogle Scholar
  6. 6.
    Dawn, B., Xuan, Y.T., Marian, M., Flaherty, M.P., Murphree, S.S., Smith, T.L., et al. (2001). Cardiac-specific Abrogation of NF-kappaB Activation in Mice by Transdominant Expression of a Mutant Ikappa-Balpha. J. Mol. Cell. Cardiol. 33(1):161–173.PubMedCrossRefGoogle Scholar
  7. 7.
    Haudek, S.B., Spencer, E., Bryant, D.D., White, D.J., Maass, D., Horton, J.W., et al. (2001). Overexpression of cardiac I-kappaBalpha prevents endotoxin-induced myocardial dysfunction. Am. J. Physiol. Heart Circ. Physiol. 280(3):H962-H968.PubMedGoogle Scholar
  8. 8.
    Haudek, S.B., Bryant, D.D., and Giroir, B.P. (2001). Differential regulation of myocardial NF kappa B following acute or chronic TNF-alpha exposure. J. Mol. Cell. Cardiol. 33(6):1263–1271.PubMedCrossRefGoogle Scholar
  9. 9.
    Kubota, T., Miyagishima, M., Frye, C., Alber, F., Bounoutas, G., Kadokami, T., et al. (2001). Overexpression of tumor necrosis alpha activates both anti- and pro-apoptotic pathways in the myocardium. JMCC 33:1331–1344.Google Scholar
  10. 10.
    Knuefermann, P., Chen, P., Misra, A., Shi, S.P., Abdellatif, M., and Sivasubramanian, N. (2002). Myotrophin/V-1, a protein up-regulated in the failing human heart and in postnatal cerebellum, converts NKkappa B p50–p65 heterodimers to p50-p50 and p65-p65 homodimers. J. Biol. Chem. 277(26):23,888–23,897.CrossRefGoogle Scholar
  11. 11.
    Parry, G. and Mackman, N. (1994). A set of inducible genes expressed by activated human monocytic and endothelial cells contain κB-like sites that specifically bind c-Rel-p65 heterodimers. J. Biol. Chem. 269:20,823–20,825.Google Scholar
  12. 12.
    Brown, K., Gerstberger, S., Carlson, L., Franzoso, G., and Siebenlist, U. (1995). Control of Ikappa B-alpha proteolysis by site-specific, signal induced phosphorylation. Science 267(5203):1485–1488.PubMedCrossRefGoogle Scholar
  13. 13.
    Scherer, D.C., Brockman, J.A., Chen, Z., Maniatis, T., and Ballard, D.W. (1995). Signal-induced degradation of Ikappa B alpha requires site-specific ubiquitination. Proc. Natl. Acad. Sci. USA 92:11,259–11,263.CrossRefGoogle Scholar
  14. 14.
    Arenzana-Seisdedos, F., Thompson, J., Rodriguez, M.S., Bachelerie, F., Thomas, D., and Hay, R.T. (1995). Inducible nuclear expression of newly synthesized I kappa B alpha negatively regulates DNA-binding and transcriptional activities of NF-kappa B. Mol. Cell Biol. 15(5): 2689–2696.PubMedGoogle Scholar
  15. 15.
    Lee, S.H. and Hannink, M. (2002). Characterization of the nuclear import and export functions of Ikappa B (epsilon). J. Biol. Chem. 277(26):23,358–23,366.CrossRefGoogle Scholar
  16. 16.
    Shimada, T., Kawai, T., Takeda, K., Matsumoto, M., Inoue, J., Tatsumi, Y., et al. (1999). IKK-I, a novel lipopolysaccharide inducible kinase that is related to IkappaB kinases. Int. Immunol. 11:1357–1362.PubMedCrossRefGoogle Scholar
  17. 17.
    Huynh, Q.K., Boddupalli H., Rouw, S.A., Koboldt, C.M., Hall, T., Sommers, C., et al. (2000). Characterization of the recombinant IKK1/IKK2 heterodimer. Mechanisms regulating kinase activity. J. Biol. Chem. 275(34):25,883–25,891.CrossRefGoogle Scholar
  18. 18.
    Peters, R.T., Liao, S.M., and Maniatis, T. (2000) IKK-epsilon is part of a novel PMA-inducible Ikappa-B kinase complex. Mol. Cell 5:513–522.PubMedCrossRefGoogle Scholar
  19. 19.
    Zhang, S.Q., Kovalenko, A., Cantarella, G., and Wallach, D. (2000). Recruitment of the IKK signalosome to the p55 TNF receptor: RIP and A20 bind to NEMO (IKK gamma) upon receptor stimulation. Immunity 12(3):301–311.PubMedCrossRefGoogle Scholar
  20. 20.
    Abu-Amer, Y., Ross, F.P., McHugh, K.P., Livolsi, A., Peyron, J.-F., and Teitelbaum, S.L. (1998). Tumor necrosis factor-α activation of nuclear transcription factor-κB in marrow macrophages is mediated by c-Src tyrosine phosphorylation of IκBα. JBC 273(45):29,417–29,423.CrossRefGoogle Scholar
  21. 21.
    Diaz-Guerra, M.J., Castrillo, A., Martin-Sanz, P., and Bosca, L. (1999). Negative regulation by protein tyrosine phosphatase of IFN-gamma-dependent expression of inducible nitric oxide synthase. J Immunol. 162(11):6776–6783.PubMedGoogle Scholar
  22. 22.
    Livolsi, A, Busuttil, V., Imbert, V., Abraham, R.T., and Peyron, J.F. (2001). Tyrosine phosphorylation-dependent activation of NF-kappa B. Requirement for p56 LCK and ZAP-70 protein tyrosine kinases. Eur. J. Biochem. 268: 1508–1515.PubMedCrossRefGoogle Scholar
  23. 23.
    Suyang, H., Phillips, R., Douglas, I., and Ghosh, S. (1996). Role of unphosphorylated, newly synthesized I kappa B beta in persistent activation of NF-kappa B. Mol. Cell Biol. 16(10):5444–5449.PubMedGoogle Scholar
  24. 24.
    Baeuerle, P. and Henkel, T. (1994). Function and activation of NF-κB in the immune system. Annu. Rev. Immunol. 12:141–179.PubMedGoogle Scholar
  25. 25.
    Siebenlist, U., Franzoso, G., and Brown, K. (1994). Structure, regulation and function of NF-κB. Annu. Rev. Cell Biol. 10:405–455.PubMedCrossRefGoogle Scholar
  26. 26.
    Sen, S., Kundu, G, Mekhail, N., Castrel, J., Misonon, K., and Healy, B. (1990). Myotrophin: purification of a novel peptide from spontaneously hypertensive rat heart that influences myocardial growth. J. Biol. Chem. 265 (27):16,635–16,643.Google Scholar
  27. 27.
    Sivasubramanian, N., Adhikary, G., Sil, P.C., Sen, S. (1996). Cardiac myotrophin exhibits rel/NE-kappa B interacting activity in vitro. J. Biol. Chem. 271(5):2812–2816.PubMedCrossRefGoogle Scholar
  28. 28.
    Yang, Y., Rao, N.S., Walker, E., Sen, S., and Qin, J. (1997). Nuclear magnetic resonance assignment and secondary structure of an ankyrin-like repeat-bearing protein: myotrophin. Protein Sci. 6(6):1347–1351.PubMedGoogle Scholar
  29. 29.
    Vermeulin, L., De Wilde, G., Notebaert, S., Berghe, W.V., and Haegeman, G. (2002). Regulation of the transcriptional activity of the nuclear factor-κB p65 subunit. Biochem. Pharmacol. 64:963–970.CrossRefGoogle Scholar
  30. 30.
    Frantz, B. Nordby, E.C., Bren, G., Steffan, N., Paya, C.V., Kincaid, R.L., et al. (1994). Calcineurin acts in synergy with PMA to inactivate I kappa B/MAD3, an inhibitor of NF-kappa B. EMBO J. 13(4):861–870.PubMedGoogle Scholar
  31. 31.
    Steffan, N.M., Bren, G.D., Frantz, B., Tocci, M.J., O'Neill, E.A., and Paya, C.V. (1995). Regulation of IkB alpha phosphorylation by PKC- and Ca(2+)-dependent signal transduction pathways. J. Immunol. 155(10):4685–4691.PubMedGoogle Scholar
  32. 32.
    Kanno, T. and Siebenlist, U. (1996). Activation of nuclear factor-kappaB via T cell receptor requires a Raf kinase and Ca2+ influx. Functional synergy between Raf and calcineurin. J. Immunol. 157(12):5277–5283.PubMedGoogle Scholar
  33. 33.
    Yang, J., Fan, G.H., Wadzinski, B.E., Sakurai, H., and Richmond, A. (2001). Protein phosphatase 2A interacts with and directly dephosphorylates Re1A. J. Biol. Chem. 276(51):47,828–47,833.Google Scholar
  34. 34.
    Shumway, S.D., Berchtold, C.M., Gould, M.N., and Miyamoto, S. (2002). Evidence for unique calmodulin-dependent nuclear factor-kappaB regulation in WEHI-231 B cells. Mol. Pharmacol. 61(1):177–185.PubMedCrossRefGoogle Scholar
  35. 35.
    Chen, L.F., Mu, Y., and Greene, W.C. (2002). Acetylation of RelA at discrete sites regulates distinct nuclear functions of NF-kappaB EMBO J. 21(23):6539–6548.PubMedCrossRefGoogle Scholar
  36. 36.
    Furia, B., Deng, L., Wu, K., Baylor S., Kehn, K., Li, H., et al. (2002). Enhancement of nuclear factor-kappa B acetylation by coactivator p300 and HIV-1 Tat proteins. J. Biol. Chem. 277(7):4973–4980.PubMedCrossRefGoogle Scholar
  37. 37.
    Kiernan, R., Bres, V., Ng, R.W., Coudart, M.P., El Messaoudi, S., Sardet, C., et al. (2003). Post-activation turnoff of NF-kappa B-dependent transcription is regulated by acetylation of p65. J. Biol. Chem. 278(4):2758–2766.PubMedCrossRefGoogle Scholar
  38. 38.
    Janssen-Heininger, Y.M., Poynter M.E., and Baeuerle, P.A. (2000). Recent advances towards understanding redox mechanisms in the activation of nuclear factor κB. Free Rad. Biol. Med. 28(9):1317–1327.PubMedCrossRefGoogle Scholar
  39. 39.
    Collart, M.A., Baeuerle, P., and Vassalli, P. (1990). Regulation of tumor necrosis factor alpha transcription in macrophages: involvement of four kappa B-like motifs and of constitutive and inducible forms of NF-kappa B. Mol. Cell Biol. 10(4):1498–1506.PubMedGoogle Scholar
  40. 40.
    Shakhov, A.N., Collart, M.A., Vassalli, P., Nedospasov, S.A., and Jongeneel, C.V. (1990). Kappa B-type enhancers are involved in lipopolysaccharide-mediated transcriptional activation of the tumor necrosis factor alpha gene in primary macrophages. J. Exp. Med. 171(1):35–47.PubMedCrossRefGoogle Scholar
  41. 41.
    Hiscott, J., Marois, J., Garoufalis, J., D'Addario, M., Roulston, A., Kwan, I., et al. (1993). Characterization of a functional NF-kappa B site in the human interleukin 1 beta promoter: evidence for a positive autoregulatory loop. Mol. Cell Biol. 13(10):6231–6240.PubMedGoogle Scholar
  42. 42.
    Yamamoto, K., Arakawa, T., Ueda, N., and Yamamoto, S. (1995). Transcriptional roles of nuclear factor kappa B and nuclear factor-interleukin-6 in the tumor necrosis factor alpha-dependent induction of cyclooxygenase-2 in MC3T3-E1 cells. J. Biol. Chem. 270(52):31,315–31,320.Google Scholar
  43. 43.
    Pan, J. and McEver, R.P. (1995). Regulation of the human P-selectin promoter by Bcl-3 and specific homodimeric members of the NF-kappa B/Rel family. J. Biol. Chem. 270(39):23,077–23,083.Google Scholar
  44. 44.
    Chilov, D. Kukk, E., Taira, S., Jeltsch, M., Kaukonen, J., Palotie, A., et al. (1997). Genomic organization of human and mouse genes for vascular endothelial growth factor C. J. Biol. Chem. 272(40):25,176–25,183.CrossRefGoogle Scholar
  45. 45.
    Kinugawa, K., Shimizu, T., Yao, A., Kohmoto, O., Serizawa, T., and Takahashi, T. (1997). Transcriptional regulation of inducible nitric oxide synthase in cultured neonatal rat cardiac myocytes. Circ. Res. 81:911–921.PubMedGoogle Scholar
  46. 46.
    Yin, L., Hubbard, A.K., and Giardina, C. (2000). NF-kappa B regulates transcription of the mouse telomerase catalytic subunit. J. Biol. Chem. 275(47):36,671–36,675.CrossRefGoogle Scholar
  47. 47.
    Catz, S.D. and Johnson, J.L. (2001). Transcriptional regulation of bcl-2 by nuclear factor kappa B and its significance in prostate cancer. Oncogene 20(50):7342–7351.PubMedCrossRefGoogle Scholar
  48. 48.
    Kishimoto, I., Rossi, K., and Garbers, D.L. (2001). A genetic model provides evidence that the receptor for atrial natriuretic peptide (guanylyl cyclase-A) inhibits cardiac ventricular myocyte. Proc. Natl. Acad. Sci. USA 98(5): 2703–2706.PubMedCrossRefGoogle Scholar
  49. 49.
    Kubota, T., Miyagishima, M., Frye, C.S., Alber, S.M., Bounoutas, G.S., Kadokami, T., et al. (2001). Over-expression of tumor necrosis factor- alpha activates both anti- and pro-apoptotic pathways in the myocardium. J. Mol. Cell. Cardiol. 33(7):1331–1344.PubMedCrossRefGoogle Scholar
  50. 50.
    Ikeda, U., Maeda, Y., Yamamoto, K., and Shimada, K. (2002). C-Reactive protein augments inducible nitric oxide synthase expression in cytokine-stimulated cardiac myocytes. Cardiovasc. Res. 56(1):86–92.PubMedCrossRefGoogle Scholar
  51. 51.
    Tian, B., Nowak, D.E., Jamaluddin, M., Wang, S., and Brasier, A.R. (2005). Identification of direct genomic targets downstream of the NF-kappa B transcription factor mediating TNF signaling. J. Biol. Chem. [Epub ahead of print].Google Scholar
  52. 52.
    Wang, D. and Baldwin, A.S. Jr. (1998). Activation of nuclear factor-kappaB-dependent transcription by tumor necrosis factor-alpha is mediated through phosphorylation of Re1A/p65 on serine 529. J. Biol. Chem. 273(45): 29,411–29,416.Google Scholar
  53. 53.
    Sakurai, H., Chiba, H., Miyoshi, H., Sugita, T., and Toruimi, W. (1999). IκB kinases phosphorylate NF-κB p65 subunit on serine 536 in the transactivation domain. IBC 274:30,353–30,356.Google Scholar
  54. 54.
    Sizemore, N., Lerner, N., Dombrowski, N. Sakurai, H., and Stark, G.R. (2002). Distinct roles of the Ikappa B kinase alpha and beta subunits in liberating nuclear factor kappa B (NF-kappa B) from Ikappa B and in phosphorylating the p65 subunit of NF-kappa B. J. Biol. Chem. 277 (6):3863–3869.PubMedCrossRefGoogle Scholar
  55. 55.
    McKay, L.I. and Cidlowski, J.A. (2000). CBP (CREB binding protein) integrates NF-kappaB (nuclear factor-kappaB) and glucocorticoid receptor physical interactions and antagonism. Mol. Endocrinol. 14(8):1222–1234.PubMedCrossRefGoogle Scholar
  56. 56.
    Cogswell, J.P., Godlevski, M.M., Wisely, G.B., Clay, W.C., Leesnitzer, L.M., Ways, J.P., et al. (1994). NF-kappa B regulates IL-1 beta transcription through a consensus NF-kappa B binding site and a nonconsensus CRE-like site. J. Immunol. 153(2):712–723.PubMedGoogle Scholar
  57. 57.
    Yie, J., Senger, K., and Thanos, D. (1999). Mechanism by which the IFN-beta enhanceosome activates transcription. Proc. Natl. Acad. Sci. USA 96(23):13,108–13,113.CrossRefGoogle Scholar
  58. 58.
    Munshi, N., Yie, Y., Merika, M., Senger, K., Lomvardas, S., Agalioti, T., et al. (1999). The IFN-beta enhancer: a paradigm for understanding activation and repression of inducible gene expression. Cold Spring Harb. Symp. Quant. Biol. 64:149–159.PubMedCrossRefGoogle Scholar
  59. 59.
    Casolaro, V., Georas, S.N., Song, Z., Zubkoff, I.D., Abdulkadir, S.A., Thanos, D., et al. (1995). Inhibition of NF-AT-dependent transcription by NF-kappa B: implications for differential gene expression in T helper cell subsets. Proc. Natl. Acad. Sci. USA 92(25):11,623–11,627.CrossRefGoogle Scholar
  60. 60.
    Tsuboi, A., Muramatsu, M., Tsutsumi, A., Arai, K., and Arai, N. (1994). Calcineurin activates transcription from the GM-CSF promoter in synergy with either protein kinase C or NF-kappa B/AP-1 in T cells. Biochem. Biophys. Res. Commun. 199(2):1064–1072.PubMedCrossRefGoogle Scholar
  61. 61.
    Sica, A., Dorman, L., Viggiano, V., Cippitelli, M., Ghosh, P., Rice, N., and Young, H.A. (1997). Interaction of NF-kappaB and NFAT with the interferon-gamma promoter. J. Biol. Chem. 272(48):30,412–30,420.CrossRefGoogle Scholar
  62. 62.
    Tian, B., Zhang, Y., Luxon, B.A., Garofalo, R.P., Casola, A., Sinha, M., et al. (2002). Identification of NF-kappaB-dependent gene networks in respiratory syncytial virus-infected cells. J. Virol. 76(13):6800–6814.PubMedCrossRefGoogle Scholar
  63. 63.
    Tian, B. and Brasier, A.R. (2003). Identification of a nuclear factor kappa B-dependent gene network. Recent Prog. Horm. Res. 58:95–30.PubMedCrossRefGoogle Scholar
  64. 64.
    Autieri, M.V., Yue, T.L., Ferstein G.Z., and Ohlstein, E. (1995). Antisense oligonucleotides to the p65 subunit of NF-κB inhibit human vascular smooth muscle cell adherence and proliferation and prevent neointima formation in rat carotid arteries. Biochem. Biophys. Res. Commun. 213(3):827–836.PubMedCrossRefGoogle Scholar
  65. 65.
    Kubota, T., McTiernan, C.F., Frye, C.S., Slawson, S.E., Lemster, B.H., Koretsky, A.P., et al. (1997). Dilated cardiomyopathy in transgenic mice with cardiac-specific overexpression of tumor necrosis factor-alpha. Circ. Res. 81(4): 627–635.PubMedGoogle Scholar
  66. 66.
    Cooper, M., Lindholm, P., Peiper, G., Seibel, R., Moore, G., Nakanishi, A., et al. (1998). Myocardial nuclear factor-κB activity and nitric oxide production in rejecting cardiac allografts. Transplantation 66:838–844.PubMedCrossRefGoogle Scholar
  67. 67.
    Wong, S.C., Fukuchi, M., Melnyk, P., Rodger, I., and Giaid, A. (1998). Induction of cyclooxygenase-2 and activation of NF-κB in myocardium of patients with congestive heart failure. Circulation 98:100–103.PubMedGoogle Scholar
  68. 68.
    Bauriedel, G., Hutter, R., Welsch, U., Bach, R., Sievert, H. and Luderitz, B. (1999). Role of smooth muscle cell death in advanced coronary primary lesions: implications for plaque instability. Cardiovasc. Res. 41:480–488.PubMedCrossRefGoogle Scholar
  69. 69.
    Erl, W., Hansson, G.K., de Martin, R., Draude, G., Weber, K.S., and Weber, C. (1999). Nuclear factor-kappa B regulates induction of apoptosis and inhibitor of apoptosis protein-1 expression in vascular smooth muscle cells. Circ. Res. 84(6):668–677.PubMedGoogle Scholar
  70. 70.
    Li, Y.Y., McTiernan, C.F., and Feldman, A.M (1999). Proinflammatory cytokines regulate tissue inhibitors of metalloproteinases and disintegrin metalloproteinase in cardiac cells. Cardiovasc. Res. 42(1):162–172.PubMedCrossRefGoogle Scholar
  71. 71.
    Ortego, M., Bustos, C., Hernandez-Presa, M.A., Tunon, J., Diaz, C., Hernandez, G., et al. (1999). Atorvastatin reduces NF-kappaB activation and chemokine expression in vascular smooth muscle cells and mononuclear cells. Atherosclerosis 147(2):253–261.PubMedCrossRefGoogle Scholar
  72. 72.
    Sasaki, H., Galang, N., and Maulik, N. (1999). Redox regulation of NF-kappaB and AP-1 in ischemic reperfused heart. Antioxid. Redox Signal. 1(3):317–324.PubMedCrossRefGoogle Scholar
  73. 73.
    Maulik, N., Sasaki, H., Addya, S., and Das, D.K. (2000). Regulation of cardiomyocyte apoptosis by redox-sensitive transcription factors. FEBS Lett. 485(1):7–12.PubMedCrossRefGoogle Scholar
  74. 74.
    Hayashi, K., Takahata, H., Kitagawa, N., Kitange, G., Kaminogo, M., and Shibata, S. (2001). N-acetylcysteine inhibited nuclear factor-kappaB expression and the intimal hyperplasia in rat carotid arterial injury. Neurol. Res. 23(7):731–738.PubMedCrossRefGoogle Scholar
  75. 75.
    Li, C., Kao, R.L., Ha, T., Kelley, J., Browder, I.W., and Williams, D.L. (2001) Early activation of IKKbeta during in vivo myocardial ischemia. Am. J. Physiol. Heart Circ. Physiol. 280(3):H1264-H1271.PubMedGoogle Scholar
  76. 76.
    Purcell, N.H., Tang, G., Yu, C., Mercurio, F., DiDonato, J.A., and Lin, A. (2001). Activation of NF-κB is required for hypertrophic growth of primary rat neonatal ventricular cardiomyocytes. PNAS 98(12):6668–6673.PubMedCrossRefGoogle Scholar
  77. 77.
    Breuss, J.M., Cejna, M., Bergmeister, H., Kadl, A., Baumgartl, G., Steurer, S., et al. (2002). Activation of nuclear factor-kappa B significantly contributes to lumen loss in a rabbit iliac artery balloon angioplasty model. Circulation 105(5):633–638.PubMedCrossRefGoogle Scholar
  78. 78.
    Hirotani, S., Otsu, K., Nishida, K., Higuchi, Y., Morita, T., Nakayama, H., et. al. (2002). Involvement of nuclear factor-kappaB and apoptosis signal-regulating kinase 1 in G-protein-coupled receptor agonist-induced cardiomyocyte hypertrophy. Circulation 105(4):509–515.PubMedCrossRefGoogle Scholar
  79. 79.
    Higuchi, Y., Otsu, K., Nishida, K., Hirotani, S., Nakayama, H., Yamaguchi, O., et al. (2002). Involvement of reactive oxygen species-mediated NF-kappa B activation in TNF-alpha-induced cardiomyocyte hypertrophy. J. Mol. Cell. Cardiol. 34(2):233–240.PubMedCrossRefGoogle Scholar
  80. 80.
    Brown, M. and Jones, W.K. (2004). NF-κB action in sepsis: the innate immune system and the heart. Front. Biosci. 9:1201–1217.PubMedCrossRefGoogle Scholar
  81. 81.
    Gupta, S., Young, D., and Sen, S. (2005). Inhibition of NF-kappaB induces regression of cardiac hypertrophy, independent of blood pressur control, in spontaneously hypertensive rats. Am. J. Physiol Heart Circ. Physiol. [Epub ahead of print].Google Scholar
  82. 82.
    Peng, M., Huang, L., Xie, Z.J., Huang, W.H., and Askari, A. (1995). Oxidant-induced activations of nuclear factor-kappa B and activator protein-1 incardiac myocytes. Cell. Mol. Biol. Res. 41(3):189–197.PubMedGoogle Scholar
  83. 83.
    Canty, T.G., Jr., Boyle, E.M., Jr., Farr, A., Morgan, E.N., Verrier, E.D., and Pohlman, T.H. (1999). Oxidative stress induces NF-kappaB nuclear translocation without degradation of IkappaB alpha. Circulation 100(19 Suppl.): II361-II364.PubMedGoogle Scholar
  84. 84.
    Wei, Z., Costa, K., Al-Mehdi, A.B., Dodia, C., Muzykantov, V., and Fisher, A.B. (1999). Simulated ischemia in flow-adapted endothelial cells leads to generation of reactive oxygen species and cell signaling. Circ. Res. 85(8):682–689.PubMedGoogle Scholar
  85. 85.
    Bergmann, M.W., Loser, P., Dietz, R., and von Harsdorf, R. (2001). Effect of NF-kappa B inhibition on TNF-alpha-induced apoptosis and downstream pathways in cardiomyocytes. J. Mol. Cell. Cardiol. 33(6)1223–1232.PubMedCrossRefGoogle Scholar
  86. 86.
    Cowling, R.T., Gurantz, D., Peng, J., Dillmann, W.H., and Greenberg, B.H. (2002). Transcription factor NF-kappa B is necessary for up-regulation of type 1 angiotensin II receptor mRNA in rat cardiac fibroblasts treated with tumor necrosis factor-alpha or interleukin-1 beta. J. Biol. Chem. 277(8):5719–5724.PubMedCrossRefGoogle Scholar
  87. 87.
    Wang, Z., Castresana, M.R., Detmer, K. and Newman, W.H. (2002) An IkappaB-alpha mutant inhibits cytokine gene expression and proliferation in human vascular smooth muscle cells. J. Surg. Res. 102(2):198–206.PubMedCrossRefGoogle Scholar
  88. 88.
    Maulik, N., Sato, M., Price, B.D., and Das, D.K. (1998). An essential role of NFkappaB in tyrosine kinase signaling of p38 MAP kinase regulation of myocardial adaptation to ischemia. FEBS Lett. 429(3):365–369.PubMedCrossRefGoogle Scholar
  89. 89.
    Xuan, Y.T., Tang, X.L., Banerjee, S., Takano, H., Li, R.C., Han, H., et al. (1999). Nuclear factor-kappaB plays an essential role in the late phase of ischemic preconditioning in conscious rabbits, Circ. Res. 84(9):1095–1109.PubMedGoogle Scholar
  90. 90.
    Zhao, X. and Eghbali-Webb, M. (2002) Gender-related differences in basal and hypoxia-induced activation of signal transduction pathways controlling cell cycle progression and apoptosis, in cardiac fibroblasts. Endocrine 18(2):137–145.PubMedCrossRefGoogle Scholar
  91. 91.
    Mustapha, S., Kirshner, A., De Moissac, D., and Kirshenbaum, L.A. (2000). A direct requirement of nuclear factor-kappa B for suppression of apoptosis in ventricular myocytes. Am. J. Physiol. Heart Circ. Physiol. 279(3):H939-H945.PubMedGoogle Scholar
  92. 92.
    Irem, S.O., Eyer, C.L., Smith, J.R., and Anderson, A.C. (1991). Protective effects of selected sulfhydryl containing compounds against global ischemia in isolated perfused rat hearts. Proc. West. Pharmacol. Soc. 34:161–165.PubMedGoogle Scholar
  93. 93.
    Morishita, R., Sugimoto, T., Aoki, M., Kida, I., Tomita, N., Moriguchi, A., et al. (1997). In vivo transfection of cis element “decoy” against nuclear factor-kappaB binding site prevents myocardial infarction. Nat. Med. 3(8):894–899.PubMedCrossRefGoogle Scholar
  94. 94.
    Brown, M., McGuinness, M., Wright, T., Ren, X., Wang, Y., Boivin, G. P., et al. (2005). Cardiac-specific blockade of NF-κB in cardiac pathophysiology: differences between acute and chronic stimuli in vivo. Feb 4; Epub ahead of print, PMID: 15695559.Google Scholar
  95. 95.
    Bing, R.J. (2001) Some aspects of, biochemistry of myocardial infarction. Cell. Mol. Life Sci. 58(3):351–355.PubMedCrossRefGoogle Scholar
  96. 96.
    Valen, G., Yan, Z.Q., and Hansson, G.K. (2001). Nuclear factor kappa-B and the heart. J. Am. Coll. Cardiol. 38(2): 307–314.PubMedCrossRefGoogle Scholar
  97. 97.
    Chandrasekar, B., Streitman, J.E., Colston, J.T., and Freeman, G.L. (1998). Inhibition of nuclear factor kappa B attenuates proinflammatory cytokine and inducible nitricoxide synthase expression in postischemic myocardium. Biochim. Biophys. Acta 1406(1):91–106.PubMedGoogle Scholar
  98. 98.
    Biagini, G., Sala, D., and Zini, I., (1995). Diethyldithiocarbamate, a superoxide dismutase inhibitor, counteracts the maturation of ischemic-like lesions caused by endothelin-1 intrastrial injection. Neurosci. Lett. 190(3):212–216.PubMedCrossRefGoogle Scholar
  99. 99.
    Sawa, Y., Morishita, R., Suzuki, K., Kagissaki, K., Kaneda, Y., Maeda, K., et al. (1997). A novel strategy for myocardial protection using in vivo transfection of cis element ‘decoy’ against NFkappaB binding site: evidence for a role of NFkappaB in ischemia-reperfusion injury. Circulation 96(9 Suppl.):II—280—4.Google Scholar
  100. 100.
    Zhang, D., Jiang, S.L., Rzewnicki, D., Samols, D., and Kushner, I. (1995). The effect of interleukin-1 on C-reactive protein expression in Hep3B cells is exerted at the transcriptional level. Biochem. J. 310(Pt 1): 143–148.PubMedGoogle Scholar
  101. 101.
    Brasier, A.R., Ron, D., Tate, J.E., and Habener, J.F. (1990). A family of constitutive C/EBP-like DNA binding proteins attenuate the IL-1 alpha induced. NF kappa B mediated trans-activation of the angiotensiongen gene acute-phase response element. EMBO J. 9(12):3933–3944.PubMedGoogle Scholar
  102. 102.
    Valen, G., Paulsson, G., and Vaage, J. (2001). Induction of inflammatory mediators during reperfusion of the human heart. Ann. Thorac. Surg. 71(1):226–232.PubMedCrossRefGoogle Scholar
  103. 103.
    Balligand, J.L., Ungureanu-Longrois, D., Simmons, W.W., Pimental, D., Malinski, T.A., Kapturczak, M., et al. (1994). Cytokine-inducible nitric oxide synthase (iNOS) expression in cardiac myocytes. Characterization and regulation of iNOS expression and detection of iNOS activity in single cardiac myocytes in vitro. J. Biol. Chem. 269:27,580–27,588.Google Scholar
  104. 104.
    Misra, A., Haudek, S.B., Knuefermann, P., Vallejo, J.G., Chen, Z.J., Michael, L.H., et al. (2003). Nuclear factorkappaB protects the adult cardiac myocyte against ischemia-induced apoptosis in a murine model of acute myocardial infarcition. Circulation 108(25):3075–3078.PubMedCrossRefGoogle Scholar
  105. 105.
    Subramaniam, A, Jones, W.K., Gulick, J., Wert, S., Neuman, J., and Robbins, J. (1991). Tissue-specific regulation of the α-myosin heavy chain gene promoter in transgenic mice. J. Biol. Chem. 266:24,613–24,620.Google Scholar
  106. 106.
    Irwin, M. W., Mak, S., Mann, D. L., Qu, R., Penninger, J. M., Yan, Y., et al. (1999). Tissue expression and immunolocalization of tumor necrosis factor-alpha in, postinfarction dysfunctional myocardium. Circulation 99:1492–1498.PubMedGoogle Scholar
  107. 107.
    Maekawa, N., Wada, H., Kanda, T., Niwa, T., Yamada, Y., Saito, K., et al. (2002). Improved myocardial ischemia/reperfusion injury in mice lacking tumor necrosis factoralpha. J. Am. Coll. Cardiol. 39(7):1229–1235.PubMedCrossRefGoogle Scholar
  108. 108.
    Kurrelmeyer, K. M., Michael, L. H., Baumgarten, G., Taffet, G. E., Peschon, J. J., Sivasubramanian, N., et al. (2000). Endogenous tumor necrosis factor protects the adult cardiac myocyte against ischemic-induced apoptosis in a murine model of acute myocardial infarction. PNAS 97 (10):5456–5461.PubMedCrossRefGoogle Scholar
  109. 109.
    Higuchi, Y., McTiernan, C. F., Frye, C. B., McGowan, B. S., Chan, T. O., and Feldman, A. M. (2004). Tumor neocrosis factor receptors 1 and 2 differentially regulate survival, cardiac dysfunction, and remodeling in transgenic mice with tumor, necrosis factor-alpha-induced cardiomyopathy. Circulation 109(15):1892–1897.PubMedCrossRefGoogle Scholar
  110. 110.
    Ren, X., Wang, Y., and Jones, W. K. (2004). TNF-alpha is required for late ischemic preconditioning but not for remote preconditioning of trauma. J. Surg. Res. 121:120–129.PubMedCrossRefGoogle Scholar
  111. 111.
    Hoffman, A., Levchenko, A., Scott, M. L., and Baltimore, D. (2002). The IκB-NF-κB signaling module: temporal control and selective gene activation. Science 298:1241–1245.CrossRefGoogle Scholar
  112. 112.
    Lipniacki, T., Paszek, P., Brasier, A. R., Luxon, B., and Kimmel, M. (2004). Mathematical model of NF-kappaB regulatory module. J. Theor. Biol. 228(2):195–215.PubMedCrossRefGoogle Scholar
  113. 113.
    Chandrasekar, B. and Freemen, G. L. (1997). Induction of nuclear factor-kappaB and activation factor 1 in post-ischemic myocardium. FEBS Lett. 401:30–34.PubMedCrossRefGoogle Scholar
  114. 114.
    Lille, S. T., Lefler, S. R., Mowlavi, A., Suchy, H., Boyle, E. M. Jr., Farr, A. L., Su, C. Y., Frank, N., and Mulligan, D. C. (2001). INhibition of the initial wave of NF-kappaB activity in rat muscle reduces ischemia/reperfusion injury. Muscle Nerve 24(4):534–541.PubMedCrossRefGoogle Scholar
  115. 115.
    Ladner, K. J., Caligiuri, M. A., and Guttridge, D. C. (2003). Tumor necrosis factor-regulated biphasic activation of NF-kaapa B is required for cytokine-induced loss of skeletal muscle gene products. J. Biol. Chem. 278(4):2294–2303.PubMedCrossRefGoogle Scholar
  116. 116.
    Nelson, D. E., Ihekwaba, A. E., Elliott, M., Johnson, J. R., Gibney, C. A., Foreman, B. E., et al. (2004). Oscillations in NF-kappaB signaling control the dynamics of gene expression. Science 306(5696):704–708.PubMedCrossRefGoogle Scholar
  117. 117.
    Lee, E. G., Boone, D. L., Chai, S., Libby, S. L., Chien, M., Lodoice, J. P., et al. (2002). Failure to regulate TNF-induced NF-κB and cell death responses in A20-deficient mice. Science 289:2350–2354.CrossRefGoogle Scholar
  118. 118.
    Krikos, A., Laherty, C. D., and Dixit, V. M. (1992). Transcriptional activation og the tumor necrosis factor alphainducible zinc finger protein, A20, is mediated by kappa B elements. JBC 267:17,971–17,976.Google Scholar
  119. 119.
    Arvelo, M. B., Cooper, J. T., Longo, C., Soizic, D., Grey, S. T., Mahiou, J., et al. (2002). A20 protects mice from D-galactosamine/lipopolysaccharide acute toxic lethal hepatitis. Hepatology 35:535–543.PubMedCrossRefGoogle Scholar
  120. 120.
    Fishbein, M. C., Meerbaum, S., Rit, J., Lando, U., Kanmatsuse, K., Mercier, J. C., et al. (1981). Early phase acute myocardial infarct size quantification: validation of the triphenyl tetrazolium chloride tissue enzyme staining technique. Am. Heart J. 101(5):593–596.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2005

Authors and Affiliations

  • W. Keith Jones
    • 1
  • Maria Brown
    • 1
  • Michael Wilhide
    • 1
  • Suiwen He
    • 1
  • Xiaoping Ren
    • 1
  1. 1.Department of Pharmacology and Cell BiophysicsUniversity of CincinnatiCincinnati

Personalised recommendations