Abstract
The mammalian thioredoxins are a family of small redox proteins that undergo NADPH dependent reduction by thioredoxin reductase. Reduced thioredoxins reduce oxidized cysteine groups on proteins including transcription factors to increase their binding to DNA, and is a source of reducing equivalents for enzymes such as thioredoxin peroxidase which removes H2O2and alkyl peroxides. Thioredoxin-1 is over expressed in many human tumors where it is associated with aggressive tumor growth, inhibited apoptosis and decreased patient survival. Transfection of cells with thioredoxin-1 has been shown to increase cell growth and inhibit apoptosis. We have used DNA micro array to investigate the effects of thioredoxin-1 transfection on the expression of a panel of 520 redox, apoptosis and cell growth related genes in MCF-7 human breast cancer cells. One of the genes whose expression was increased as a result of thioredoxin-1 over expression was thioredoxin peroxidase-2. This increase was confirmed by Northern blotting. Transfection of mouse WEHI7.2 thymoma cells with human thioredoxin peroxidase-2 was found to protect the cells from apoptosis induced by H2O2but not from apoptosis induced by dexamethasone, doxorubicin or etoposide. Thus, increased thioredoxin peroxidase-2 expression does not explain the widespread antiapoptotic effects of thioredoxin-1.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Baker, A., Payne, C.M., Briehl, M.M. and Powis, G. (1997) Thioredoxin, a gene found overexpressed in human cancer, inhibitis apoptosis in vitro and in vivo.Cancer Res 57: 5162–5167.
Baker, A.F., Briehl, M.M., Dorr, R. and Powis, G. (1996) Decreased antioxidant defense and increased oxidant stress during dexamethasone-induced apoptosis: bcl-2 selectively prevents the loss of catalase activity. Cell Death Differ 3: 207–213.
Berggren, M., Gallegos, A., Gasdaska, J.R., Gasdaska, P.Y., Warneke, J. and Powis, G. (1996) Thioredoxin and thioredoxin reductase gene expression in human tumors and cell lines, and the effects of serum stimulation and hypoxia. Anticancer Res 16: 3459–3466.
Berggren, M., Gallegos, A., Gasdaska, J. and Powis, G. (1997) Cellular thioredoxin reductase activity is regulated by selenium. Anticancer Res 17: 3377–3380.
Chae, H.Z., Chung, S.J. and Rhee, S.G. (1994) Thioredoxin-dependent peroxide reductase from yeast. J. Biol. Chem 269: 27670–27678.
Deiss, L.P. and Kimchi, A. (1991) A genetic tool used to identify thioredoxin as a mediator of a growth inhibitory signal. Science 252: 117–120.
Ericson, M.L., Hörling, J., Wendel-Hansen, V., Holmgren, A. and Rosen, A. (1992) Secretion of thioredoxin after in vitro activation of human B cells. Lymphokine Cytokine Res 11: 201–207.
Follmann, H. and Haberlein, I. (1995) Thioredoxins: Universal, yet specific thiol-disulfide redox cofactors. BioFactors 5: 147–156.
Freemerman, A.J., Gallegos, A. and Powis, G. (1999) NF-kappaB transactivation is increased but not involved in the proliferative effects of thioredoxin overexpression in MCF-7 breast cancer cells. Cancer Res 59: 4090–4094.
Freemerman, A.J. and Powis, G. (2000) Redox-inactive thioredoxin enhances drug-induced apoptosis. Leukemia
Fujii, S., Nanbu, Y., Nonogaki, H., Konishi, I., Mori, T., Masutani, H. and Yodoi, J. (1991) Coexpression of adult T-cell leukemia-derived factor, a human thioredoxin homologue, and human papillomavirus DNA in neoplastic cervical squamous epithelium. Cancer 68: 1583–1591.
Gallegos, A., Gasdaska, J.R., Taylor, C.W., Paine-Murrieta, G.D., Goodman, D., Gasdaska, P.Y., Berggren, M., Briehl, M.M. and Powis, G. (1996) Transfection with human thioredoxin increases cell proliferation and a dominant negative mutant thioredoxin reverses the transformed phenotype of breast cancer cells. Cancer Res 56: 5765–5770.
Gallegos, A., Berggren, M., Gasdaska, J.R. and Powis, G. (1997) Mechanisms of the regulation of thioredoxin reductase activity in cancer cells by the chemopreventive agent selenium. Cancer Res 57: 4965–4970.
Gallegos, A., Raffel, J., Bhattacharyya, A.K. and Powis, G. (2000) Increased expression of thioredoxin in human primary and metastatic colon cancer. American Association for Cancer Research 41: 189
Gasdaska, J.R., Harney, J.W., Gasdaska, P.Y., Powis, G. and Berry, M.J. (1999) Regulation of human thioredoxin reductase expression and activity by 3’-untranslated region selenocysteine insertion sequence and mRNA instability elements. J.Biol.Chem 274: 25379–25385.
Gasdaska, P.Y., Oblong, J.E., Cotgreave, I.A. and Powis, G. (1994) The predicted amino acid sequence of human thioredoxin is identical to that of the autocrine growth factor human adult T-cell derived factor (ADF): Thioredoxin mRNA is elevated in some human tumors. Biochim.Biophys.Acta 1218: 292–296.
Gasdaska, P.Y., Gasdaska, J.R., Cochran, S. and Powis, G. (1995) Cloning and sequencing of human thioredoxin reductase. FEBS Lett 373: 5–9.
Gasdaska, P.Y., Berggren, M.M., Berry, M.J. and Powis, G. (1999) Cloning, sequencing and functional expression of a novel human thioredoxin reductase. FEBS Lett 442: 105–111.
Grogan, T.M., Fenoglio-Prieser, C., Zeheb, R., Bellamy, W., Frutiger, Y., Vela, E., Stemmerman, G., MacDonald, J., Richter, L., Gallegos, A. and Powis, G. (2000) Thioredoxin, a puntative oncogene product, is overexpressed in gastric carcinoma and associated with increased proliferation and increased cell survival. Human Pathol 31: 475–481.
Hayashi, T., Ueno, Y. and Okamoto, T. (1993) Oxidoreductive regulation of nuclear factor kappaB: Involvement of a cellular reducing catalyst thioredoxin. J.Biol.Chem 268: 11380–11388.
Hirotsu, S., Abe, Y., Okada, K., Nagahara, N., Hori, H., Nishino, T. and Hakoshima, T. (1999) Crystal structure of a multifunctional 2-Cys peroxiredoxin heme-binding protein 23 kDa/proliferation-associated gene product. Proc.Natl.Acad.Sci. USA 96:12333–12338.
Jin, D., Zoon, H.J., Rhee, S.G. and Jeang, K. (1997) Regulatory role for a novel human thioredoxin peroxidase in NF-kappaB activation. J. Biot. Chem 272: 30952–30961.
Kang, S.W., Chae, H.Z., Seo, M.S., Kim, K., Baines, I.C. and Rhee, S.G. (1998) Mammalian peroxidoxin isoforms can reduce hydrogen peroxide generated in response to growth factors and tumor necrosis factor-α. J.Biol.Chem 273: 6297–6302.
Kawahara, N., Tanaka, T., Yokomizo, A., Nanri, H., Ono, M., Wada, M., Kohno, K., Takenaka, K., Sugimachi, K. and Kuwano, M. (1996) Enhanced coexpression of thioredixin and high mobility group protein 1 genes in human hepatocellular carcinoma and the possible association with decreased sensitivity to cisplatin. Cancer Res 56: 5330–5333.
Laurent, T.C., Moore, E.C. and Reichard, P. (1964) Enzymatic synthesis of deoxyribonucleotides VI. Isolation and characterization of thioredoxin, the hydrogen donor from Escherichia coli B. J.Biol.Chem 239: 3436–3444.
Lee, S., Kim, J., Kwon, K., Yoon, H.W., Levine, R.L., Ginsburg, A. and Rhee, S.G. (1999) Molecular cloning and characterization of a mitochondrial selenocysteine-containing thioredoxin reductase from rat liver. J.Biol.Chem 274: 4722–4734.
Matsumoto, A., Okado, A., Fujii, T., Fujii, J., Egashira, M., Niikawa, N. and Taniguchi, N. (1999) Cloning of the peroxiredoxin gene family in rats and characterization of the fourth member. FEBS Lett 443: 246–250.
Miranda-Vizueta, A. (1999) TrxR3, a novel human thioredoxin reductase. GenBank Accession AF133519: bp 1–2165
Miranda-Vizuete, A., Damdimopoulos, A.E., Pedrajas, J.R., Gustafsson, J.-A. and Spyrou, G. (1999) Human mitochondrial thioredoxin reductase. cDNA cloning, expression and genomic organization. Eur.J. Biochem 261: 405–411.
Mustacich, D., Coon, A. and Powis, G. (2000) Nuclear targeted thioredoxin transforms NIH 3T3 cells. American Association for Cancer Research 41: 189
Mustacich, D. and Powis, G. (2000) Thioredoxin reductase. Biochem.J 346: 1–8.
Nakamura, H., Masutani, H., Tagaya, Y., Yamauchi, A., Inamoto, T., Nanbu, Y., Fujii, S., Ozawa, K. and Yodoi, J. (1992) Expression and growth-promoting effect of adult T-cell leukemia-derived factor. A human thioredoxin homologue in hepatocellular carcinoma. Cancer 69: 2091–2097.
Nakamura, H., Nakamura, K. and Yodoi, J. (1997) Redox regulation of cellular activation. Annu. Rev. Immunol 15: 351–369.
Nakamura, H., Bai, J., Nishinaka, Y., Ueda, S., Sasada, T., Ohshio, G., Imamura, M., Takabayashi, A., Yamaoka, Y. and Yodoi, J. (2000) Expression of thioredoxin and glutaredoxin, redox-regulating proteins, in pancreatic cancer. Cancer Detection and Prevention 24: 53–60.
Nishiyama, A., Ohno, T., Iwata, S., Matsui, M., Hirota, K., Masutani, H., Nakamura, H. and Yodoi, J. (1999) Demonstration of the interaction of thioredoxin with p40phox, a phagocyte oxidase component, using a yeast two-hybrid system. Immunol.Lett 68: 155–159.
Pahl, P., Berger, R., Hart, I., Chae, H.Z., Rhee, S.G. and Patterson, D. (1995) Localization of TDPX1, a human homologue of the yeast thioredoxin-dependent peroxide reductase gene (TPX) to chromosome 13q12. Genomics 26: 602–606.
Peddie, C.M., Wolf, C.R., McLellan, L.I., Collins, A.R. and Bown, D.T. (1997) Oxidative DNA damage in CD34+ myelodysplastic cells is associated with intracellular redox changes and elevated plasma tumor necrosis factor-a concentration. Br.J.Haematol 99: 625–630.
Powis, G., Mustacich, D. and Coon, A. (2000) The role of the redox protein thioredoxin in cell growth and cancer. Free Rad.Biol.&Med (In Press)
Prosperi, M., Ferbus, D., Karczinski, I. and Goubin, G. (1993) A human cDNA corresponding to a gene overexpressed during cell proliferation encodes a product sharing homology with amoebic and bacterial proteins. J.Biol.Chem 268: 11050–11056.
Redl, B., Merschak, P., Abt, B. and Wojnar, P. (1999) Phage display reveals a novel interaction of human tear lipocalin and thioredoxin which is relevant for ligand binding. FEBS Lett 460: 182–186.
Saitoh, M., Nishitoh, H., Fujii, M., Takeda, K., Tobiume, K., Sawada, Y., Kawabata, M., Miyazono, K. and Ichijo, H. (1998) Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. The EMBO Journal 17: 2596–2606.
Shau, H., Butterfield, L.H., Chiu, R. and Kim, A. (1994) Cloning and sequence analysis of candidate human nautral killer-enhancing factor genes. Immunogenetics 40: 129–134.
Shau, H., Kim, A.T., Hedrick, C.C., Lusis, A.J., Tompkins, C., Finney, R., Leung, D.W. and Paglia, D.E. (1997) Endogenous natural killer enhancing factor-B increases cellular resistance to oxidative stresses. Free Rad. Biol. &Med 22: 497–507.
Silverman, R.B. and Nandi, D.L. (1988) Reduced thioredoxin: A possible physiological cofactor for vitamin K epoxide reductase. Further support for an active site disulfide. Biochem. Biophys. Res. Commun 155: 1248–1254.
Spyrou, G., Enmark, E., Miranda-Vizuete, A. and Gustafsson, J. (1997) Cloning and expression of a novel mammalian thioredoxin. J.Biol.Chem 272: 2936–2941.
Ueno, M., Masutani, H., Jun Arai, R., Yamauchi, A., Hirota, K., Sakai, T., Inamoto, T., Yamaoka, Y., Yodoi, J. and Nikaido, T. (2000) Thioredoxin-dependent redox regulation of p53-mediated p21 activation. J.Biol.Chem 274: 35809–35815.
Watabe, S., Kohno, H., Kouyama, H., Hiroi, T., Yago, N. and Nakazawa, T. (1994) Purification and characterization of a substrate protein for mitochondrial ATP-dependent protease in boue adrenal cortex. J. Biochem 115: 648–654.
Watson, J.A., Rumsby, M.G. and Wolowacz, R.G. (1999) Phage dispaly identifies thioredoxin and superoxide dismutase as novel protein kinase C-interacting proteins: thioredoxin inhibits protein kinase C-mediated phosphorylation of histone. Biochem.J 343: 301–305.
Zhang, P., Liu, B., Kang, S.W., Seo, M.S., Rhee, S.G. and Obeid, L.M. (1997) Thioredoxin peroxidase is a novel inhibitor of apoptosis with a mechanism distinct from that of Bc1–2.J. Biol. Chem 272: 30615–30618.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2001 Springer Science+Business Media New York
About this chapter
Cite this chapter
Husbeck, B., Berggren, M.I., Powis, G. (2001). DNA Microarray Reveals Increased Expression of Thioredoxin Peroxidase in Thioredoxin-1 Transfected Cells and Its Functional Consequences. In: Dansette, P.M., et al. Biological Reactive Intermediates VI. Advances in Experimental Medicine and Biology, vol 500. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0667-6_21
Download citation
DOI: https://doi.org/10.1007/978-1-4615-0667-6_21
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4613-5185-6
Online ISBN: 978-1-4615-0667-6
eBook Packages: Springer Book Archive