Skip to main content
SpringerLink
Log in

Redox Control of Signal Transduction, Gene Expression and Cellular Senescence

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Reactive oxygen species (ROS) act as subcellular messengers in such complex cellular processes as mitogenic signal transduction, gene expression, regulation of cell proliferation, replicative senescence, and apoptosis. They serve to maintain cellular homeostasis and their production is under strict control. However, the mechanisms whereby ROS act are still obscure. Here we review recent advances in our understanding of signaling mechanisms and recent data about the involvement of ROS in: (i) the regulation of the mitogenic transduction elements, particularly protein kinases and phosphatases; (ii) the regulation of gene expression; and (iii) the induction of replicative senescence and the role, if any, in aging and age-related disorders.

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

Similar content being viewed by others

References

  1. Sundaresan, M., Yu, Z. X., Ferrans, V. J., Irani, K., and Finkel, T. 1995. Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Science 270:296–299.

    PubMed  Google Scholar 

  2. Bae, Y. S., Sung, J. Y., Kim, O. S., Kim, Y. J., Hur, K. C., Kazlauskas, A., and Rhee, S. G. 2000. Platelet-derived growth factor-induced H2O2 production requires the activation of phosphatidylinositol 3-kinase. J. Biol. Chem. 275:10527–10531.

    PubMed  Google Scholar 

  3. Ammendola, R., Ruocchio, M., Chirico, G., Russo, L., De Felice, C., Esposito, F., Russo, T., and Cimino, F. 2002. Inhibition of NADH/NADPH oxidase affects signal transduction by growth factor receptors in normal fibroblasts. Arch. Biochem. Biophys. 397:253–257.

    PubMed  Google Scholar 

  4. Kamata, H., Shibukawa, Y., Oka, S. I., and Hirata, H. 2000. Epidermal growth factor receptor is modulated by redox through multiple mechanisms: Effects of reductants and H2O2. Eur. J. Biochem. 267:1933–1944.

    PubMed  Google Scholar 

  5. Heffetz, D., Bushkin, I., Dror, R., and Zick, Y. 1990. The insulinomimetic agents H2O2 and vanadate stimulate protein tyrosine phosphorylation in intact cells. J. Biol. Chem. 265:2896–2902.

    PubMed  Google Scholar 

  6. Nishida, M., Maruyama, Y., Tanaka, R., Kontani, K., Nagao, T., and Kurose, H. 2000. G alpha(i) and G alpha(o) are target proteins of reactive oxygen species. Nature 408:492–495.

    PubMed  Google Scholar 

  7. Ushio-Fukai, M., Alexander, R. W., Akers, M., Yin, Q., Fujio, Y., Walsh, K., and Griendling, K. K. 1999. Reactive oxygen species mediate the activation of Akt/protein kinase B by angiotensin II in vascular smooth muscle cells. J. Biol. Chem. 274:22699–22704.

    PubMed  Google Scholar 

  8. Mukhin, Y. V., Garnovskaya, M. N., Collinsworth, G., Grewal, J. S., Pendergrass, D., Nagai, T., Pinckney, S., Greene, E. L., and Raymond, J. R. 2000. 5-Hydroxytryptamine1A receptor/gibetagamma stimulates mitogen-activated protein kinase via NAD(P)H oxidase and reactive oxygen species upstream of src in chinese hamster ovary fibroblasts. Biochem. J. 347:61–67.

    PubMed  Google Scholar 

  9. Pani, G., Colavitti, R., Bedogni, B., Anzevino, R., Borrello, S., and Galeotti, T. 2000. A redox signaling mechanism for density-dependent inhibition of cell growth. J. Biol. Chem. 275:38891–38899.

    PubMed  Google Scholar 

  10. Bedogni, B., Pani, G., Colavitti, R., Riccio, A., Borrello, S., Murphy, M., Smith, R., Eboli, M. L., and Galcotti, T. 2003. Redox regulation of CREB and induction of manganous superoxide dismutase in NGF-dependent cell survival. J. Biol. Chem. 278:16510–16519.

    PubMed  Google Scholar 

  11. Hirata, H., Hibasami, H., Yoshida, T., Ogawa, M., Matsumoto, M., Morita, A., and Uchida, A. 2001. Nerve growth factor signaling of p75 induces differentiation and ceramide-mediated apoptosis in Schwann cells cultured from degenerating nerves. Glia 36:245–258.

    PubMed  Google Scholar 

  12. Lee, S. Y., Andoh, T., Murphy, D. L., and Chiuch, C. C. 2003. 17beta-Estradiol activates ICI 182,780-sensitive estrogen receptors and cyclic GMP-dependent thioredoxin expression for neuroprotection. FASEB J. 17:947–948.

    PubMed  Google Scholar 

  13. Finkel, T. 2003. Oxidant signals and oxidative stress. Curr. Opin. Cell Biol. 15:247–254.

    PubMed  Google Scholar 

  14. Bae, Y. S., Kang, S. W., Seo, M. S., Baines, I. C., Tekle, E., Chock, P. B., and Rhee, S. G. 1997. Epidermal growth factor (EGF)-induced generation of hydrogen peroxide: Role in EGF receptor-mediated tyrosine phosphorylation. J. Biol. Chem. 272:217–221.

    PubMed  Google Scholar 

  15. Datta, S. R., Brunet, A., and Greenberg, M. E. 1999. Cellular survival: A play in three Akts. Genes Dev. 13:2905–2927.

    PubMed  Google Scholar 

  16. Devary, Y., Gottlieb, R. A., Smeal, T., and Karin, M. 1992. The mammalian ultraviolet response is triggered by activation of Src tyrosine kinases. Cell 71:1081–1091.

    PubMed  Google Scholar 

  17. Yoshizumi, M., Abe, J., Haendeler, J., Huang, Q., and Berk, B. C. 2000. Src and Cas mediate JNK activation but not ERK1/2 and p38 kinases by reactive oxygen species. J. Biol. Chem. 275:11706–11712.

    PubMed  Google Scholar 

  18. Secrist, J. P., Burns, L. A., Karnitz, L., Koretzsly, G. A., and Abraham, R. T. 1993. Stimulatory effects of the protein tyrosine phosphatase inhibitor, pervanadate, on T-cell activation events. J. Biol. Chem. 268:5886–5393.

    PubMed  Google Scholar 

  19. Hardwick, J. S. and Sefton, B. M. 1997. The activated form of the Lck tyrosine protein kinase in cells exposed to hydrogen peroxide is phosphorylated at both Tyr-394 and Tyr-505. J. Biol. Chem. 272:25429–25432.

    PubMed  Google Scholar 

  20. Wang, X., McCullough, K. D., Franke, T. F., and Holbrook, N. J. 2000. Epidermal growth factor receptor-dependent Akt activation by oxidative stress enhances cell survival. J. Biol. Chem. 275:14624–14631.

    PubMed  Google Scholar 

  21. Mitsuuchi, Y., Johnson, S. W., Selvakumaran, M., Williams, S. J., Hamilton, T. C., and Testa, J. R. 2000. The phosphatidylinositol 3-kinase/AKT signal transduction pathway plays a critical role in the expression of p21WAF1/CIP1/SDI1 induced by cisplatin and paclitaxel. Cancer Res. 60:5390–5394.

    PubMed  Google Scholar 

  22. Esposito, F., Chirico, G., Montesano Gesualdi, N., Posada, I., Ammendola, R., Russo, T., Cirino, G., and Cimino, F. 2003. Akt activation by reactive oxygen species is independent from tyrosine kinase receptor phosphorylation and requires Src activity. J. Biol. Chem. 278:20828–20834.

    PubMed  Google Scholar 

  23. Chang, L. and Karin, M. 2001. Mammalian MAP kinase signalling cascades. Nature 410:37–40.

    PubMed  Google Scholar 

  24. Zafarullah, M., Li, W. Q., Sylvester, J., and Ahmad, M. 2003. Molecular mechanisms of N-acetylcysteine actions. Cell Mol. Life Sci. 60:6–20.

    PubMed  Google Scholar 

  25. Guyton, K. Z., Liu, Y., Gorospe, M., Xu, Q., and Holbrook, N. J. 1996. Activation of mitogen-activated protein kinase by H2O2: Role in cell survival following oxidant injury. J. Biol. Chem. 271:4138–4142.

    PubMed  Google Scholar 

  26. Esposito, F., Russo, T., and Cimino, F. 2002. Generation of prooxidant conditions in intact cells to induce modifications of cell cycle regulatory proteins. Methods Enzymol. 352:258–268.

    PubMed  Google Scholar 

  27. Russo, T., Zambrano, N., Esposito, F., Ammendola, R., Cimino, F., Fiscella, M., O'Connor, P. M., Jackman, J., Anderson, C. W., and Appella, E. 1995. A p53-independent pathway for activation of WAF1/CIP1 expression following oxidative stress. J. Biol. Chem. 270:29386–29391.

    PubMed  Google Scholar 

  28. Gupta, K., Kashirsagar, S., Li, W., Gui, L., Ramakrishnan, S., Gupta, P., Law, P. Y., and Hebbel, R. P. 1999. VEGF prevents apoptosis of human microvascular endothelial cells via opposing effects on MAPK/ERK and SAPK/JNK signaling. Exp. Cell Res. 247:495–504.

    PubMed  Google Scholar 

  29. Esposito, F., Cuccovillo, F., Vanoni, M., Cimino, F., Anderson, C. W., Appella, E., and Russo, T. 1997. Redox-mediated regulation of p21waf1/cip1 expression involves a post-transcriptional mechanism and activation of the mitogen-activated protein kinase pathway. Eur. J. Biochem. 245:730–737.

    PubMed  Google Scholar 

  30. Porcile, C., Stanzione, S., Piccioli, P., Bajetto, A., Barbero, S., Bisaglia, M., Bonavia, R., Florio, T., and Schettini, G. 2003. Pyroolidinedithiocarbamate induces apoptosis in cerebelar granule cells: Involvement of AP-1 and MAP kinases. Neurochem. Int. 43:31–38.

    PubMed  Google Scholar 

  31. Herrera, B., Fernandez, M., Roncero, C., Ventura, J. J., Porras, A., Valladares, A., Benito, M., and Fabregat, I. 2001. Activation of p38MAPK by TGF-beta in fetal rat hepatocytes requires radical oxygen production, but is dispensable for cell death. FEBS Lett. 499:225–229.

    PubMed  Google Scholar 

  32. Ushio-Fukai, M., Alexander, R. W., Akers, M., and Griedling, K. K. 1998. p38 Mitogen-activated protein kinase is a critical component of the redox-sensitive signaling pathways activated by angiotensin II: Role in vascular smooth muscle cell hypertrophy. J. Biol. Chem. 273:15022–15029.

    PubMed  Google Scholar 

  33. Kamata, H. and Hirata, H. 1999. Redox regulation of cellular signalling. Cell. Signal. 11:1–14.

    PubMed  Google Scholar 

  34. Fisher, E. H., Charbonneau, H., and Tonks, N. K. 1991. Protein tyrosine phosphatases: A diverse family of intracellular and transmembrane enzymes. Science 253:401–406.

    PubMed  Google Scholar 

  35. Hecht, D. and Zick, Y. 1992. Selective inhibition of protein tyrosine phosphatase activities by H2O2 and vanadate in vitro. Biochem. Biophys. Res. Commun. 188:773–779.

    PubMed  Google Scholar 

  36. Lee, S. R., Kwon, K. S., Kim, S. R., and Rhee, S. G. 1998. Reversible inactivation of protein-tyrosine phosphatase 1B in A431 cells stimulated with epidermal growth factor. J. Biol. Chem. 273:15366–15372.

    PubMed  Google Scholar 

  37. Elchebly, M., Payette, P., Michaliszyn, E., Cromlish, W., Collins, S., Loy, A. L., Normandin, D., Cheng, A., Himms-Hagen, J., Chan, C. C., Ramachandran, C., Gresser, M. J., Tremblay, M. L., Kennedy, B. P. 1999. Increased insulin sensitivity and obesity resistance in mice lacking the protein tyrosine phosphatase-1B gene. Science 283:1544–1548.

    PubMed  Google Scholar 

  38. Meng, T. C., Fukada, T., and Tonks, N. 2002. Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo. Mol. Cell 9:387–399.

    PubMed  Google Scholar 

  39. Esposito, F., Cuccovillo, F., Russo, L., Casella, F., Russo T., and Cimino, F. 1998. A new p21waf1/cip1 isoform is an early event of cell response to oxidative stress. Cell Death Differ. 5:940–945.

    PubMed  Google Scholar 

  40. Esposito, F., Russo, L., Russo, T., and Cimino, F. 2000. Retinoblastoma protein dephosphorylation is an early event of cellular response to prooxidant conditions. FEBS Lett. 470:211–215.

    PubMed  Google Scholar 

  41. Dyson, N. 1998. The regulation of E2F by pRB-family proteins. Genes Dev. 12:2245–2262.

    PubMed  Google Scholar 

  42. Cimino, F., Esposito, F., Ammendola, R., and Russo, T. 1997. Gene regulation by reactive oxygen species. Curr. Top. Cell. Regul. 35:123–148.

    PubMed  Google Scholar 

  43. Ammendola, R., Mesuraca, M., Russo, T., and Cimino, F. 1994. The DNA-binding efficiency of Sp1 is affected by redox changes. Eur. J. Biochem. 225:483–489.

    PubMed  Google Scholar 

  44. Esposito, F., Cuccovillo, F., Morra, F., Russo, T., and Cimino, F. 1995. DNA binding activity of the glucocorticoid receptor is sensitive to redox changes in intact cells. Biochim. Biophys. Acta 1260:308–314.

    PubMed  Google Scholar 

  45. Ammendola, R., Mesuraca, M., Russo, T. and Cimino, F. 1992. Sp1 DNA binding efficiency is highly reduced in nuclear extracts from aged rat tissues. J. Biol. Chem. 267:17944–17948.

    PubMed  Google Scholar 

  46. Hutchison, K. A., Matic, G., Meshinchi, S., Bresnick, E. H., and Pratt, W. B. 1991. Redox manipulation of DNA binding activity and BuGR epitope reactivity of the glucocorticoid receptor. J. Biol. Chem. 266:10505–10509.

    PubMed  Google Scholar 

  47. Esposito, F., Agosti, V., Morrone, G., Morra, F., Cuomo, C., Russo, T., Venuta, S., and Cimino, F. 1994. Inhibition of the differentiation of human myeloid cell lines by redox changes induced through glutathione depletion. Biochem. J. 301:649–653.

    PubMed  Google Scholar 

  48. Ho, E. and Ames, B. N. 2002. Low intracellular zinc induces oxidative DNA damage, disrupts p53, NFkappa B, and AP1 DNA binding, and affects DNA repair in a rat glioma cell line. Proc. Natl. Acad. Sci. USA 99:16770–16775.

    PubMed  Google Scholar 

  49. Makino, Y., Okamoto, K., Yoshikawa, N., Aoshima, M., Hirota, K., Yodoi, J., Umesono, K., Makino, I., and Tanaka, H. 1996. Thioredoxin: A redox-regulating cellular cofactor for glucocorticoid hormone action—Cross talk between endocrine control of stress response and cellular antioxidant defense system. J. Clin. Invest. 98:2469–2477.

    PubMed  Google Scholar 

  50. Hainaut, P. and Milner, J. 1993. Redox modulation of p53 conformation and sequence-specific DNA binding in vitro. Cancer Res. 53:4469–4473.

    PubMed  Google Scholar 

  51. Hollstein, M., Sidransky, D., Vogelstein, B., and Harris, C. C. 1991. p53 mutations in human cancers. Science 253:49–53.

    PubMed  Google Scholar 

  52. De Vries, E., Ricke, D. O., De Vries, T. N., Hartmann, A., Blaszyk, H., Liao, D., Soussi, T., Kovach, J. S., and Sommer, S. 1996. Database of mutations in the p53 and APC tumor suppressor genes designed to facilitate molecular epidemiological analyses. Hum. Mutat. 7:202–213.

    PubMed  Google Scholar 

  53. Jayaraman, L., Murthy, K. G., Zhu, C., Curran, T., Xanthoudakis, S., and Prives, C. 1997. Identification of redox/repair protein Ref-1 as a potent activator of p53. Genes Dev. 11:558–570.

    PubMed  Google Scholar 

  54. Gaiddon, C., Moorthy, N. C., and Prives, C. 1999. Ref-1 regulates the transactivation and pro-apoptotic functions of p53 in vivo. EMBO J. 18:5609–5621.

    PubMed  Google Scholar 

  55. Tanaka, T., Nakamura, H., Nishiyama, A., Hosoi, F., Masutani, H., Wada, H., and Yodoi, J. 2001. Redox regulation by thioredoxin superfamily: Protection against oxidative stress and aging. Free Radic. Res. 33:851–855.

    PubMed  Google Scholar 

  56. Swada, M., Nakashima, S., Kiyono, T., Nakagawa, M., Yamada, J., Yamakawa, H., Banno, Y., Shinoda, J., Nishimura, Y., Nozawa, Y., Sakai, N. 2001. p53 regulates ceramide formation by neutral sphingomyelinase through reactive oxygen species in human glioma cells. Oncogene 20:1368–1378.

    PubMed  Google Scholar 

  57. Drane, P., Bravard, A., Bouvard, V., and May, E. 2001. Reciprocal down-regulation of p53 and SOD2 gene expression: Implication in p53 mediated apoptosis. Oncogene 20:430–439.

    PubMed  Google Scholar 

  58. Xanthoudakis, S. and Curran, T. 1996. Redox regulation of AP-1: A link between transcription factor signaling and DNA repair. Adv. Exp. Med. Biol. 387:69–75.

    PubMed  Google Scholar 

  59. Hill, C. S. and Treisman, R. 1995. Transcriptional regulation by extracellular signals: Mechanisms and specificity. Cell 80:199–211.

    PubMed  Google Scholar 

  60. Treisman, R. 1995. Journey to the surface of the cell: Fos regulation and the SRE. EMBO J. 14:4905–4913.

    PubMed  Google Scholar 

  61. Adler, V., Yin, Z., Fuchs, S. Y., Benezra, M., Rosario, L., Tew, K. D., Pincus, M. R., Sardana, M., Henderson, C. J., Wolf, C. R., Davis, R. J., Ronai, Z. 1999. Regulation of JNK signaling by GSTp. EMBO J. 18:1321–1334.

    PubMed  Google Scholar 

  62. Abate, C., Patel, L., Rauscher, F. J. III, and Curran, T. 1990. Redox regulation of fos and jun DNA-binding activity in vitro. Science 249:1157–1161.

    PubMed  Google Scholar 

  63. Freemerman, A. J., Gallegos, A., and Powis, G. 1999. Nuclear factor kappaB transactivation is increased but is not involved in the proliferative effects of thioredoxin overexpression in MCF-7 breast cancer cells. Cancer Res. 59:4090–4094.

    PubMed  Google Scholar 

  64. Hirota, K., Matsui, M., Iwata, S., Nishiyama, A., Mori, K., and Yodoi, J. 1997. AP-1 transcriptional activity is regulated by a direct association between thioredoxin and Ref-1. Proc. Natl. Acad. Sci. USA 94:3633–3638.

    PubMed  Google Scholar 

  65. Zen, K., Karsan, A., Stempien-Otero, A., Yee, E., Tupper, J., Li, X., Eunson, T., Kay, M. A., Wilson, C. B., Winn, R. K., and Harlan, J. M. 1999. NF-kappaB activation is required for human endothelial survival during exposure to tumor necrosis factor-alpha but not to interleukin-1beta or lipopolysaccharide. J. Biol. Chem. 274:28808–28815.

    PubMed  Google Scholar 

  66. Bellas, R. E., Lee, J. S., and Sonenshein, G. E. 1995. Expression of a constitutive NF-kappa B-like activity is essential for proliferation of cultured bovine vascular smooth muscle cells. J. Clin. Invest. 96:2521–2527.

    PubMed  Google Scholar 

  67. Kaltschmidt, B., Sparna, T., and Kaltschmidt, C. 1999. Activation of NF-kappa B by reactive oxygen intermediates in the nervous system. Antioxidant Redox Signal. 1:129–144.

    Google Scholar 

  68. Sen, C. K. and Packer, L. 1996. Antioxidant and redox regulation of gene transcription. FASEB J. 10:709–720.

    PubMed  Google Scholar 

  69. Manna, S. K., Zhang, H. J., Yan, T., Oberley, L. W., and Aggarwal, B. B. 1998. Overexpression of manganese superoxide dismutase suppresses tumor necrosis factor-induced apoptosis and activation of nuclear transcription factor-kappaB and activated protein-1. J. Biol. Chem. 273:13245–13254.

    PubMed  Google Scholar 

  70. Wang, X., Martindale, J. L., Liu, Y., and Holbrook, N. J. 1998. The cellular response to oxidative stress: Influences of mitogen-activated protein kinase signalling pathways on cell survival. Biochem. J. 333:291–300.

    PubMed  Google Scholar 

  71. Meyer, M., Schreck, R., and Bauerle, P. A. 1993. H2O2 and antioxidants have opposite effects on activation of NF-kappa B and AP-1 in intact cells: AP-1 as secondary antioxidant-responsive factor. EMBO J. 12:2005–2015.

    PubMed  Google Scholar 

  72. Toledano, M. B. and Leonard, W. J. 1991, Modulation of transcription factor NF-kappa B binding activity by oxidation-reduction in vitro. Proc. Natl. Acad. Sci. USA 88:4328–4332.

    PubMed  Google Scholar 

  73. Hirota, K., Murata, M., Sachi, Y., Nakamura, H., Takeuchi, J., Mori, K., and Yodoi, J. 1999. Distinct roles of thioredoxin in the cytoplasm and in the nucleus: A two-step mechanism of redox regulation of transcription factor NF-kappaB. J. Biol. Chem. 274:27861–27897.

    Google Scholar 

  74. Li, N. and Karin, M. 1999. Is NF-kappaB the sensor of oxidative stress? FASEB J. 13:1137–1143.

    PubMed  Google Scholar 

  75. Gius, D., Botero, A., Shah, S., and Curry, H. A. 1999. Intracellular oxidation/reduction status in the regulation of transcription factors NF-kappaB and AP-1. Toxicol. Lett. 106:93–106.

    PubMed  Google Scholar 

  76. Skala-Rubinson, H., Vinh, J., Labas, V., Kahn, A., and Phan, D. T. 2002. Novel target sequences for Pax-6 in the brain-specific activating regions of the rat aldolase C gene. J. Biol. Chem. 277:47190–47196.

    PubMed  Google Scholar 

  77. Wang, Y., Crawford, D. R., and Davies, K. J. 1996. adapt 33: A novel oxidant-inducible RNA from hamster HA-1 cells. Arch. Biochem. Biophys. 332:255–260.

    PubMed  Google Scholar 

  78. Crawford, D. R., Lehay, K. P., Abramova, N., Lan, L., Wang, Y., and Davies, K. J. 1997. Hamster adapt78 mRNA is a Down syndrome critical region homologue that is inducible by oxidative stress. Arch. Biochem. Biophys. 342:6–12.

    PubMed  Google Scholar 

  79. Carper, D., Johnn, M., Chenn, Z., Subramaniann, S., Wangn, R., Ma, W., and Spector, A. 2001. Gene expression analysis of an H2O2-resistant lens epithelial cell line. Free Radic. Biol. Med. 31:90–97.

    PubMed  Google Scholar 

  80. Tanaka, T., Kondo, S., Iwasa, Y., Hiain, H., and Toyokunin, S. 2000. Expression of stress-response and cell proliferation genes in renal cell carcinoma induced by oxidative stress. Am. J. Pathol. 156:2149–2157.

    PubMed  Google Scholar 

  81. Ammendola, R., Fiore, F., Esposito, F., Caserta, G., Mesuraca, M., Russo, T., and Cimino, F. 1995. Differentially expressed mRNAs as a consequence of oxidative stress in intact cells. FEBS Lett. 371:209–213.

    PubMed  Google Scholar 

  82. Nickenig, G., Baudler, S., Muller, C., Werner, C., Werner, N., Welzel, H., Strehlow, K., and Bohm, M. 2002. Redox-sensitive vascular smooth muscle cell proliferation is mediated by GKLF and Id3 in vitro and in vivo. FASEB J. 16:1077–1086.

    PubMed  Google Scholar 

  83. Chinn, A. M., Ciais, D., Bailly, S., Chambaz, E., LaMarre, J., and Feige, J. J. 2002. Identification of two novel ACTH-responsive genes encoding manganese-dependent superoxide dismutase (SOD2) and the zinc finger protein TIS11b [tetradecanoyl phorbol acetate (TPA)-inducible sequence 11b]. Mol. Endocrinol. 16:1417–1427.

    PubMed  Google Scholar 

  84. Sakamoto, K., Yamasaki, Y., Kaneto, H., Fujitani, Y., Matsuoka, T., Yoshioka, R., Tagawa, T., Matsuhisa, M., Kajimoto, Y., and Hori, M. 1999. Identification of a portable repression domain and an E1A-responsive activation domain in Pax 4: A possible role of Pax4 as a transcriptional repressor in the pancreas. FEBS Lett. 461:47–51.

    PubMed  Google Scholar 

  85. Maulik, N. and Das, D. K. 1996. Molecular cloning, sequencing and expression analysis of a fatty acid transport gene in rat heart induced by ischemic preconditioning and oxidative stress. Mol. Cell Biochem.160–161:241–247.

    PubMed  Google Scholar 

  86. Bek, M. J., Wahle, S., Muller, B., Benzing, T., Huber, T. B., Kretzler, M., Cohen, C., Busse-Grawitz, A., and Pavenstadt, H. 2003. Stra13, a prostaglandin E2-induced gene, regulates the cellular redox state of podocytes. FASEB J. 17:682–684.

    PubMed  Google Scholar 

  87. Stuart, R. O., Bush, K. T., and Nigam, S. K. 2001. Changes in global gene expression patterns during development and maturation of the rat kidney. Proc. Natl. Acad. Sci. USA 98:5649–5654.

    PubMed  Google Scholar 

  88. Weindruch, R., Kayo, T., Lee, C. K., and Prolla, T. A. 2001. Microarray profiling of gene expression in aging and its alteration by caloric restriction in mice. J. Nutr. 131:918S–923S.

    PubMed  Google Scholar 

  89. Kayo, T., Allison, D. B., Weindruch, R., and Prolla, T. A. 2001. Influences of aging and caloric restriction on the transcriptional profile of skeletal muscle from rhesus monkeys. Proc. Natl. Acad. Sci. USA 98:5093–5098.

    PubMed  Google Scholar 

  90. Lee, C. K., Klopp, R. G., Weindruch, R., and Prolla, T. A. 1999. Gene expression profile of aging and its retardation by caloric restriction. Science 285:1390–1393.

    PubMed  Google Scholar 

  91. Kunsch, C. and Medford, R. M. 1999. Oxidative stress as a regulator of gene expression in the vasculature. Circul. Res. 85:753–766.

    Google Scholar 

  92. Serra, V., von Zglinicki, T., Lorenz, M., and Saretzki, G. 2003. Extracellular superoxide dismutase is a major antioxidant in human fibroblasts and slows telomere shortening. J. Biol. Chem. 278:6824–6830.

    PubMed  Google Scholar 

  93. Mandel, S., Grunblatt, E., Maor, G., and Youdim, M. B. 2002. Early and late gene changes in MPTP mice model of Parkinson's disease employing cDNA microarray. Neurochem. Res. 27:1231–1243.

    PubMed  Google Scholar 

  94. Finkel, T. and Holbrook, N. J. 2000. Oxidants, oxidative stress and the biology of ageing. Nature 408:239–247.

    PubMed  Google Scholar 

  95. Harman, D. 1981. The aging process. Proc. Natl. Acad. Sci. USA 78:7124–7128.

    PubMed  Google Scholar 

  96. Stadtman, E. R. 1992. Protein oxidation and aging. Science 257:1220–1224.

    PubMed  Google Scholar 

  97. Beckman, K. B. and Ames, B. N. 1998. The free radical theory of aging matures. Physiol. Rev. 178:547–581.

    Google Scholar 

  98. Longo, V. D. and Finch, C. E. 2003. Evolutionary medicine: From dwarf model systems to healthy centenarians? Science 299:1342–1346.

    PubMed  Google Scholar 

  99. Holzenberger, M., Dupont, J., Ducos, B., Leneuve, P., Geloen, A., Even, P. C., Cervera, P., and Le Bouc, Y. 2003. IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421:182–187.

    PubMed  Google Scholar 

  100. Nemoto, S. and Finkel, T. 2002. Redox regulation of forkhead proteins through a p66shc-dependent signaling pathway. Science 295:2450–2452.

    PubMed  Google Scholar 

  101. Furukawa-Hibi, Y., Yoshida-Araki, K., Ohta, T., Ikeda, K., and Motoyama, N. 2002. FOXO forkhead transcription factors induce G2-M checkpoint in response to oxidative stress. J. Biol. Chem. 277:26729–26732.

    PubMed  Google Scholar 

  102. Hayflick, L. 1965. The limited “in vitro” life time of human diploid cell strains. Exp. Cell Res. 37:614–636.

    PubMed  Google Scholar 

  103. Hayflick, L. and Moorhead, P. S. 1961 The serial cultivation of human diploid cell strains. Exp. Cell Res. 25:585–621.

    Google Scholar 

  104. Dimri, G. P., Lee, X., Basile, G., Acosta, M., Scott, G., Roskelley, C., Medrano, E. E., Linskens, M., Rubelj, I., Pereira-Smith, O., Peacocke, M., and Campisi, J. 1995. A biomarker that identifies senescent human cells in culture and in aging skin “in vivo.” Proc. Natl. Acad. Sci. USA 92:9363–9367.

    PubMed  Google Scholar 

  105. Campisi, J. 2000. Cancer, aging and cellular senescence. In Vivo 14:183–188.

    PubMed  Google Scholar 

  106. Wang, E. 1995. Senescent human fibroblasts resist programmed cell death, and failure to suppress bcl2 is involved. Cancer Res. 55:2284–2292.

    PubMed  Google Scholar 

  107. Campisi, J. 2001. Cellular senescence as a tumor-suppressor mechanism. Trends Cell Biol. 11:S27–S31.

    PubMed  Google Scholar 

  108. Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D., and Lowe, S. W. 1997. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88:593–602.

    PubMed  Google Scholar 

  109. Zhu, J., Woods, D., McMahon, M., and Bishop, J. M. 1998. Senescence of human fibroblasts induced by oncogenic Raf. Genes Dev. 12:2997–3007.

    PubMed  Google Scholar 

  110. Lin, A. W., Barradas, M., Stone, J. C., van Aelst, L., Serrano, M., and Lowe, S. W. 1998. Premature senescence involving p53 and p16 is activated in response to constitutive MEK/MAPK mitogenic signaling. Genes Dev. 12:3008–3019.

    PubMed  Google Scholar 

  111. Dimri, G. P., Itahana, K., Acosta, M., and Campisi, J. 2000. Regulation of a senescence checkpoint response by the E2F1 transcription factor and p14(ARF) tumor suppressor. Mol. Cell Biol. 20:273–285.

    PubMed  Google Scholar 

  112. Harley, C. B., Futcher, A. B., and Greider, C. W. 1990. Telomeres shorten during ageing of human fibroblasts. Nature 345:458–460.

    PubMed  Google Scholar 

  113. Bodnar, A. G., Ouellette, M., Frolkis, M., Holt, S. E., Chui, C. P., Morin, G. B., Harley, C. B., Shay, J. W., Lichsteiner, S., and Wright, W. E. 1998. Extension of life-span by introduction of telomerase into normal human cells. Science 279:349–352.

    PubMed  Google Scholar 

  114. Campisi, J., Dimri, G. P., and Hara, E. 1996. Control of replicative senescence. Pages 121–149, in Schneider E. and Rowe J. (ed.), Handbook of the Biology of Aging, 4th ed., Academic Press, New York.

    Google Scholar 

  115. Dimri, G. P. and Campisi, J. 1994. Molecular and cell biology of replicative senescence. Cold Spring Harb. Symp. Quant. Biol. 59:67–73.

    PubMed  Google Scholar 

  116. Stein, G. H., Beeson, M., and Gordon, L. 1990. Failure to phosphorylate the retinoblastoma gene product in senescent human fibroblasts. Science 249:666–669

    PubMed  Google Scholar 

  117. Dimri, G. P., Nakanishi, M., Desprez, P. Y., Smith, J. R., and Campisi, J. 1996. Inhibition of E2F activity by the cyclin-dependent protein kinase inhibitor p21 in cells expressing or lacking a functional retinoblastoma protein. Mol. Cell Biol. 16:2987–2997

    PubMed  Google Scholar 

  118. Schneider, E. L. and Mitsui, Y. 1976. The relationship between in vitro cellular aging and in vivo human age. Proc. Natl. Acad. Sci. USA 73:3584–3588.

    PubMed  Google Scholar 

  119. Bruce, S. A., Deadmond, S. F., and Ts'o, P. O. 1986. In vitro senescence of Syrian hamster mesenchymal cells of fetal to aged adult origin: Inverse relationship between in vivo donor age and in vitro proliferative capacity. Mech. Ageing Dev. 34:151–173.

    PubMed  Google Scholar 

  120. Smith, J. R., Pereira-Smith, O. M., and Schneider, E. L. 1978. Colony size distributions as a measure of in vivo and in vitro aging. Proc. Natl. Acad. Sci. USA 75:1353–1356.

    PubMed  Google Scholar 

  121. Allsopp, R. C., Vaziri, H., Patterson, C., Goldstein, S., Younglai, E. V., Futcher, A. B., Greider, C. W., and Harley, C. P. 1992. Telomere length predicts replicative capacity of human fibroblats. Proc. Natl. Acad. Sci. USA 89:10114–10118.

    PubMed  Google Scholar 

  122. Martin, G. M., Sprague, C. A., and Epstein, C. J. 1970. Replicative life-span of cultivated human cells: Effects of donor's age, tissue, and genotype. Lab. Invest. 23:86–92.

    PubMed  Google Scholar 

  123. Oshima, J., Campisi, J., Tannock, T. C., and Martin, G. M. 1995. Regulation of c-fos expression in senescing Werner syndrome fibroblasts differs from that observed in senescing fibroblasts from normal donors. J. Cell Physiol. 162:277–283.

    PubMed  Google Scholar 

  124. Goldstein, S. and Harley, C. B. 1979. In vitro studies of age-associated diseases. Fed. Proc. 38:1862–1867.

    PubMed  Google Scholar 

  125. Danes, B. S. 1971. Progeria: A cell culture study on aging. J. Clin. Invest. 50:2000–2003.

    PubMed  Google Scholar 

  126. Schneider, E. L. and Epstein, C. J. 1972. Replication rate and lifespan of cultured fibroblasts in Down's syndrome. Proc. Soc. Exp. Biol. Med. 141:1092–1094.

    PubMed  Google Scholar 

  127. Cristofalo, V. J., Allen, R. G., Pignolo, R. J., Martin, B. G., and Beck, J. C. 1998. Relationship between donor age and the replicative lifespan of human cells in culture: a reevaluation. Proc. Natl. Acad. Sci. USA 95:10614–10619.

    PubMed  Google Scholar 

  128. Faraonio, R., Pane, F., Intrieri, M., Russo, T., and Cimino, F. 2002. In vitro acquired cellular senescence and aging-specific phenotype can be distinguished on the basis of specific mRNA expression. Cell Death Differ. 9:862–864.

    PubMed  Google Scholar 

  129. Toussaint, O., Royer, V., Salmon, M., and Remacle, J. 2002. Stress-induced premature senescence and tissue ageing. Biochem. Pharmacol. 64:1007–1009.

    PubMed  Google Scholar 

  130. Chen, Q. and Ames, B. N. 1994. Senescence-like growth arrest induced by hydrogen peroxide in human diploid fibroblast F65 cells. Proc. Natl. Acad. Sci. USA 91:4130–4134.

    PubMed  Google Scholar 

  131. Chen, Q., Bartholomew, J. C., Campisi, J., Acosta, M., Reagen, J. D., Chen, Q. M., and Ames, B. N. 1998. Molecular analysis of H2O2-induced senescent-like growth arrest in normal human fibroblasts: p53 and Rb control G1 arrest but not cell replication. Biochem. J. 332:43–50.

    PubMed  Google Scholar 

  132. Chen, Q. M., Prowse, K. R., Tu, V. C., Purdom, S., and Linskens, M. H. 2001. Uncoupling the senescent phenotype from telomere shortening in hydrogen peroxide-treated fibroblasts. Exp. Cell Res. 265:294–303.

    PubMed  Google Scholar 

  133. Allen, R. G. and Tresini, M. 2000. Oxidative stress and gene regulation. Free Radic. Biol. Med. 28:463–499.

    PubMed  Google Scholar 

Download references

Author information

Author notes

  1. Franca Esposito

    Present address: Dipartimento di Scienze e Technologie dell Ambiente e dell Territorio, Universitá del Molize, Iseznia, Italy

Authors and Affiliations

  1. Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, Naples, Italy

    Franca Esposito, Rosario Ammendola, Raffaella Faraonio, Tommaso Russo & Filiberto Cimino

Authors
  1. Franca Esposito
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rosario Ammendola
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Raffaella Faraonio
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Tommaso Russo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Filiberto Cimino
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Filiberto Cimino.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Esposito, F., Ammendola, R., Faraonio, R. et al. Redox Control of Signal Transduction, Gene Expression and Cellular Senescence. Neurochem Res 29, 617–628 (2004). https://doi.org/10.1023/B:NERE.0000014832.78725.1a

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:NERE.0000014832.78725.1a

Search

Navigation