Abstract
Oxidative stress has been implicated in the pathogenesis of a wide variety of neuronal diseases, including ischemic neuronal injury, Alzheimer’s disease, and Parkinson’s disease. Thioredoxin reduces exposed protein disulfides and couples with peroxiredoxin to scavenge reactive oxygen species. Nerve growth factor (NGF) has profound effects on neurons, including promotion of survival and differentiation via multiple signaling pathways. As for the NGF-induced neurite outgrowth, the CREB-cAMP responsive element (CRE) pathway is important to the activation of immediate-early genes such as c-fos. Thioredoxin is upregulated by NGF through ERK and the CREB-CRE pathway in PC12 cells. Thioredoxin is necessary for NGF signaling through CRE leading to c-fos expression and also plays a critical role in the NGF-mediated neurite outgrowth in PC12 cells. Therefore, thioredoxin appears to be a neurotrophic cofactor that augments the effect of NGF on neuronal differentiation and regeneration. NGF acts also as a neuronal survival factor. Previous reports showed that thioredoxin exerts a cytoprotective effect in the nervous system. The cytoprotective effect is mediated by enhancing the action of NGF, via the regulation of antiapoptotic signaling, or through its antioxidative stress activity.
Similar content being viewed by others
References
Lo D.C. (1992) Signal transduction and regulation of neurotrophins. Curr. Opin. Neurobiol. 2, 336–340.
Huang E.J. and Reichardt L.F. (2001) Neurotrophins: roles in neuronal development and function. Annu. Rev. Neurosci. 24, 677–736.
Chao M.V. (2003) Neurotrophins and their receptors: a convergence point for many signalling pathways. Nat. Rev. Neurosci. 4, 299–309.
Greene L.A. and Tischler A.S. (1976) Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve grwoth factor. Proc. Natl. Acad. Sci. USA 73, 2424–2428.
Mobley W.C., Woo J.E., Edwards R.H., Riopelle R.J., Longo F.M., Weskamp G., et al. (1989) Developmental regulation of nerve growth factor and its receptor in the rat caudate-putamen. Neuron 3, 655–664.
Kaplan D.R., Martin-Zanca D., and Parada L.F. (1991) Tyrosine phosphorylation and tyrosine kinase activity of the trk proto-oncogene product induced by NGF. Nature 350, 158–160.
Jing S., Tapley P., and Barbacid M. (1992) Nerve growth factor mediates signal transduction through trk homodimer receptors. Neuron 9, 1067–1079.
Yao R. and Cooper G.M. (1995) Requirement for phosphatidylinositol-3 kinase in the prevention of apoptosis by nerve growth factor. Science 267, 2003–2006.
Klein R., Jing S.Q., Nanduri V., O’Rourke E., and Barbacid M. (1991) The trk proto-oncogene encodes a receptor for nerve growth factor. Cell 65, 189–197.
Gotoh Y., Nishida E., Yamashita T., Hoshi M., Kawakami M., and Sakai H. (1990) Micro-tubule-associated-protein (MAP) kinase activated by nerve growth factor and epidermal growth factor in PC12 cells. Identity with the mitogen-activated MAP kinase of fibroblastic cells. Eur. J. Biochem. 193, 661–669.
Thomas S.M., DeMarco M., D’Arcangelo G., Halegoua S., and Brugge J.S. (1992) Ras is essential for nerve growth factor- and phorbol esterinduced tyrosine phosphorylation of MAP kinases. Cell 68, 1031–1040.
Kruijer W., Schubert D., and Verma I.M. (1985) Induction of the proto-oncogene fos by nerve growth factor. Proc. Natl. Acad. Sci. USA 82, 7330–7334.
Greenberg M.E., Greene L.A., and Ziff E.B. (1985) Nerve growth factor and epidermal growth factor induce rapid transient changes in proto-oncogene transcription in PC12 cells. J. Biol. Chem. 260, 14,101–14,110.
Treisman R. (1992) The serum response element. Trends. Biochem. Sci. 17, 423–426.
Treisman R. (1995) Journey to the surface of the cell: Fos regulation and the SRE. EMBO J. 14, 4905–4913.
Sheng M., Dougan S.T., McFadden G., and Greenberg M.E. (1988) Calcium and growth factor pathways of c-fos transcriptional activation require distinct upstream regulatory sequences. Mol. Cell Biol. 8, 2787–2796.
Ginty D.D., Bonni A., and Greenberg M.E. (1994) Nerve growth factor activates a Rasdependent protein kinase that stimulates c-fos transcription via phosphorylation of CREB. Cell 77, 713–725.
Bonni A., Ginty D.D., Dudek H., and Greenberg M.E. (1995) Serine 133-phosphorylated CREB induces transcription via a cooperative mechanism that may confer specificity to neurotrophin signals. Mol. Cell Neurosci. 6, 168–183.
Hipskind R.A., Rao V.N., Mueller C.G., Reddy E.S., and Nordheim A. (1991) Ets-related protein Elk-1 is homologous to the c-fos regulatory factor p62TCF. Nature 354, 531–534.
Dalton S. and Treisman R. (1992) Characterization of SAP-1, a protein recruited by serum response factor to the c-fos serum response element. Cell 68, 597–612.
Mayr B. and Montminy M. (2001) Transcriptional regulation by the phosphorylation-dependent factor CREB. Nat. Rev. Mol. Cell Biol. 2, 599–609.
Cheng H.C., Shih H.M., and Chern Y. (2002) Essential role of cAMP-response element-binding protein activation by A2A adenosine receptors in rescuing the nerve growth factor-induced neurite outgrowth impaired by block-age of the MAPK cascade. J. Biol. Chem. 277, 33,930–33,942.
Davis S., Vanhoutte P., Pages C., Caboche J., and Laroche S. (2000) The MAPK/ERK cascade targets both Elk-1 and cAMP response element-binding protein to control long-term potentiation-dependent gene expression in the dentate gyrus in vivo. J. Neurosci. 20, 4563–4572.
Dechant G. and Neumann H. (2002) Neurotrophins. Adv. Exp. Med. Biol. 513, 303–334.
Tagaya Y., Maeda Y., Mitsui A., Kondo N., Matsui H., Hamuro J., et al. (1989) ATL-derived factor (ADF), an IL-2 receptor/Tac inducer homologous to thioredoxin; possible involvement of dithiol-reduction in the IL-2 receptor induction. (1989) EMBO J. 8, 757–764.
Wollman E.E., d’Auriol L., Rimsky L., Shaw A., Jacquot J.P., Wingfield P., et al. (1988) Cloning and expression of a cDNA for human thioredoxin. J. Biol. Chem. 263, 15,506–15,512.
Holmgren A. and Bjornstedt M. (1995) Thioredoxin and thioredoxin reductase. Methods Enzymol. 252, 199–208.
Spyrou G., Enmark E., Miranda V.A., and Gustafsson J. (1997) Cloning and expression of a novel mammalian thioredoxin. J. Biol. Chem. 272, 2936–2941.
Tanaka T., Hosoi F., Yamaguchi-Iwai Y., Nakamura H., Masutani H., Ueda S., et al. (2002) Thioredoxin-2 (TRX-2) is an essential gene regulating mitochondria-dependent apoptosis. EMBO J. 21, 1695–1703.
Fujii J. and Ikeda Y. (2002) Advances in our understanding of peroxiredoxin, a multifunctional, mammalian redox protein. Redox Rep. 7, 123–130.
Rhee S.G., Kang S.W., Chang T.S., Jeong W., and Kim K. (2001) Peroxiredoxin, a novel family of peroxidases. IUBMB Life 52, 35–41.
Matsui M., Oshima M., Oshima H., Takaku K., Maruyama T., Yodoi J., et al. (1996) Early embryonic lethality caused by targeted disruption of the mouse thioredoxin gene. Dev. Biol. 178, 179–185.
Nishiyama A., Matsui M., Iwata S., Hirota K., Masutani H., Nakamura H., et al. (1999) Identification of thioredoxin-binding protein-2/vitamin D(3) up-regulated protein 1 as a negative regulator of thioredoxin function and expression. J. Biol. Chem. 274, 21,645–21,650.
Nishinaka Y., Nishiyama A., Masutani H., Oka S., Ahsan K.M., Nakayama Y., et al. (2004) Loss of thioredoxin-binding protein-2/vitamin D3 up-regulated protein 1 in human T-cell leukemia virus type I-dependent T-cell transformation: implications for adult T-cell leukemia leukemo-genesis. Cancer Res. 64, 1287–1292.
Ichijo H., Nishida E., Irie K., ten Dijke P., Saitoh M., Moriguchi T., et al. (1997) Induction of apoptosis by ASK1, a mammalian MAP-KKK that activates SAPK/JNK and p38 signaling pathways. Science 275, 90–94.
Saito M., Nishitoh H., Fujii M., Takeda K., Tobiume K., Sawada Y., et al. (1998) Mammalian thioredoxin is a direct inhibitor of apoptosis signal-regulating kinase (ASK) 1. EMBO J. 17, 2596–2606.
Nishitoh H., Matsuzawa A., Tobiume K., Saegusa K., Takeda K., Inoue K., et al. (2002) ASK1 is essential for endoplasmic reticulum stress-induced neuronal cell death triggered by expanded polyglutamine repeats. Genes Dev. 16, 1345–1355.
Xanthoudakis S. and Curran T. (1992) Identification and characterization of Ref-1, a nuclear protein that facilitates AP-1 DNA-binding activity. EMBO J. 11, 653–665.
Hentze M.W., Rouault T.A., Harford J.B., and Klausner R.D. (1989) Oxidation-reduction and the molecular mechanism of a regulatory RNA-protein interaction. Science 244, 357–359.
Abate C., Patel L., Rauscher F.D., and Curran T. (1990) Redox regulation of fos and jun DNA-binding activity in vitro. Science 249, 1157–1161.
Xanthoudakis S., Miao G., Wang F., Pan Y.C., and Curran T. (1992) Redox activation of Fos-Jun DNA binding activity is mediated by a DNA repair enzyme. EMBO J. 11, 3323–3335.
Seki S., Akiyama K., Watanabe S., Hatsushika M., Ikeda S., and Tsutsui K. (1991) cDNA and deduced amino acid sequence of a mouse DNA repair enzyme (APEX nuclease) with significant homology to Escherichia coli exonuclease III. J. Biol. Chem. 266, 20,797–20,802.
Demple B., Herman T., and Chen D.S. (1991) Cloning and expression of APE, the cDNA encoding the major human apurinic endonuclease: definition of a family of DNA repair enzymes. Proc. Natl. Acad. Sci. USA 88, 11,450–11,454.
Xanthoudakis S., Miao G.G., and Curran T. (1994) The redox and DNA-repair activities of Ref-1 are encoded by nonoverlapping domains. Proc. Natl. Acad. Sci. USA 91, 23–27.
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.
Myrset A.H., Bostad A., Jamin N., Lirsac P.N., Toma F., and Gabrielsen O.S. (1993) DNA and redox state induced conformational changes in the DNA-binding domain of the Myb oncoprotein. EMBO J. 12, 4625–4633.
Wasylyk C. and Wasylyk B. (1993) Oncogenic conversion of Ets affects redox regulation invivo and in-vitro. Nucleic Acids Res. 21, 523–529.
Akamatsu Y., Ohno T., Hirota K., Kagoshima H., Yodoi J., and Shigesada K. (1997) Redox regulation of the DNA binding activity in transcription factor PEBP2. The roles of two conseved cysteine residues. J. Biol. Chem. 272, 14,497–14,500.
Makino Y., Okamoto K., Yoshikawa N., Aoshima M., Hirota K., Yodoi J., et al. (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.
Ueno M., Masutani H., Arai R.J., Yamauchi A., Hirota K., Sakai T., et al. (1999) Thioredoxin-dependent redox regulation of p53-mediated p21 activation. J. Biol. Chem. 274, 35,809–35,815.
Ema M.H.K., Miura J., Abe H., Yodoi J., Sogawa K., Poellinger L., et al. (1999) Molecular mechanisms of transcription activation by HLF and HIF1alpha in response to hypoxia: their stabilization and redox signal-induced interaction with CBP/p300. EMBO J. 18, 1905–1914.
Masutani H., Naito M., Takahashi K., Hattori T., Koito A., Maeda Y., et al. (1992) Dysregulation of adult T cell leukemia derived factor (ADF)/ human thioredoxin in HIV infection: Loss of ADF high producer cells in lymphoid tissues of AIDS patients. AIDS Research and Human Retroviruses 8, 1707–1715.
Wakita H., Yodoi J., Masutani H., Toda K., and Takigawa M. (1992) Immunohistochemical distribution of adult T-cell leukemia-derived factor/thioredoxin in epithelial components of normal and pathologic human skin conditions. J. Invest. Dermatol. 99, 101–107.
Sachi Y., Hirota K., Masutani H., Toda K., Okamoto T., Takigawa M., et al. (1995) Induction of ADF/TRX by oxidative stress in keratinocytes and lymphoid cells. Immunol. Lett. 44, 189–193.
Leppa S., Pirkkala L., Chow S.C., Eriksson J.E., and Sistonen L. (1997) Thioredoxin is transcriptionally induced upon activation of heat shock factor 2. J. Biol. Chem. 272, 30,400–30,404.
Kim Y.-C., Masutani H., Yamaguchi Y., Itoh K., Yamamoto M., and Yodoi J. (2001) Hemin-induced activation of the thioredoxin gene by Nrf2: A differential regulation of the antioxidant responsive element (ARE) by switch of its binding factors. J. Biol. Chem. 276, 18,399–18,406.
Balla J., Jacob H.S., Balla G., Nath K., Eaton J.W., and Vercellotti G.M. (1993) Endothelialcell heme uptake from heme proteins: induction of sensitization and desensitization to oxidant damage. Proc. Natl. Acad. Sci. USA 90, 9285–9289.
Paller M.S. and Jacob H.S. (1994) Cytochrome P-450 mediates tissue-damaging hydroxyl radical formation during reoxygenation of the kidney. Proc. Natl. Acad. Sci. USA 91, 7002–7006.
Rushmore T.H., Morton M.R., and Pickett C.B. (1991) The antioxidant responsive element. Activation by oxidative stress and identification of the DNA consensus sequence required for functional activity. J. Biol. Chem. 266, 11,632–11,639.
Friling R.S., Bensimon A., Tichauer Y., and Daniel V. (1990) Xenobiotic-inducible expression of murine glutathione S-transferase Ya subunit gene is controlled by an electrophile-responsive element. Proc. Natl. Acad. Sci. USA 87, 6258–6262.
Chui D.H., Tang W., and Orkin S.H. (1995) cDNA cloning of murine Nrf 2 gene, coding for a p45 NF-E2 related transcription factor. Biochem. Biophys. Res. Commun. 209, 40–46.
Itoh K., Igarashi K., Hayashi N., Nishizawa M., and Yamamoto M. (1995) Cloning and characterization of a novel erythroid cell-derived CNC family transcription factor heterodimerizing with the small Maf family proteins. Mol. Cell Biol. 15, 4184–4193.
Moi P., Chan K., Asunis I., Cao A., and Kan Y.W. (1994) Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region. Proc. Natl. Acad. Sci. USA 91, 9926–9930.
Kataoka K., Igarashi K., Itoh K., Fujiwara K.T., Noda M., Yamamoto M., et al. (1995) Small Maf proteins heterodimerize with Fos and may act as competitive repressors of the NF-E2 transcription factor. Mol. Cell Biol. 15, 2180–2190.
Motohashi H., Shavit J.A., Igarashi K., Yamamoto M., and Engel J.D. (1997) The world according to Maf. Nucleic Acids Res. 25, 2953–2959.
Alam J., Stewart D., Touchard C., Boinapally S., Choi A.M., and Cook J.L. (1999) Nrf2, a Cap’n’Collar transcription factor, regulates induction of the heme oxygenase-1 gene. J. Biol. Chem. 274, 26,071–26,078.
Wild A.C., Moinova H.R., and Mulcahy R.T. (1999) Regulation of γ-glutamyl cysteine synthetase subunit gene expression by the transcription factor Nrf2. J. Biol. Chem. 274, 33,627–33,636.
Aota M., Matsuda K., Isowa N., Wada H., Yodoi J., and Ban T. (1996) Protection against reperfusion-induced arrhythmias by human thioredoxin. J. Cardiovasc. Pharmacol. 27, 727–732.
Wada H., Muro K., Hirata T., Yodoi J., and Hitomi S. (1995) Rejection and expression of thioredoxin in transplanted canine lung. Chest 108, 810–814.
Wiesel P., Foster L.C., Pellacani A., Layne M.D., Hsieh C.-M., Huggins G.S., et al. (2000) Thioredoxin facilitates the induction of heme oxygenase-1 in response to inflammatory mediators. J. Biol. Chem. 275, 24,840–24,846.
Kim Y.-C., Yamaguchi Y., Kondo N., Masutani H., and Yodoi J. (2003) Thioredoxin-dependent redox regulation of the antioxidant responsive element (ARE) in electrophile response. Oncogene 22, 1860–1865.
Torocsik B., Angelastro J.M., and Greene L.A. (2002) The basic region and leucine zipper transcription factor MafK is a new nerve growth factor-responsive immediate early gene that regulates neurite outgrowth. J. Neurosci. 22, 8971–8980.
Tomimoto H., Akiguchi I., Wakita H., Kimura J., Hori K., and Yodoi J. (1993) Astroglial expression of ATL-derived factor, a human thioredoxin homologue, in the gerbil brain after transient global ischemia. Brain Res. 625, 1–8.
Mansur K., Iwahashi Y., Kiryu-Seo S., Su Q., Namikawa K., Yodoi J., et al. (1998) Up-regulation of thioredoxin expression in motor neurons after nerve injury. Brain Res. Mol. Brain Res. 62, 86–91.
Takagi Y., Horikawa F., Nozaki K., Sugino T., Hashimoto N., and Yodoi J. (1998) Expression and distribution of redox regulatory protein, thioredoxin during transient focal brain ischemia in the rat. Neurosci. Lett. 251, 25–28.
Gauntt C.D., Ohira A., Honda O., Kigasawa K., Fujimoto T., Masutani H., et al. (1994) Mitochondrial induction of adult T cell leukemia derived factor (ADF/hTx) after oxidative stresses in retinal pigment epithelial cells. Invest. Ophthalmol. Vis. Sci. 35, 2916–2923.
Ohira A., Honda O., Gauntt C.D., Yamamoto M., Hori K., Masutani H., et al. (1994) Oxidative stress induces adult T cell leukemia derived factor/thioredoxin in the rat retina. Lab. Invest. 70, 279–285.
Tanito M., Masutani H., Nakamura H., Ohira A., and Yodoi J. (2002) Cytoprotective effect of thioredoxin against retinal photic injury in mice. Invest. Ophthalmol. Vis. Sci. 43, 1162–1167.
Yamamoto M., Sato N., Tajima H., Furuke K., Ohira A., Honda Y., et al. (1997) Induction of human thioredoxin in cultured human retinal pigment epithelial cells through cyclic AMP-dependent pathway; involvement in the cytoprotective activity of prostaglandin E1. Exp. Eye Res. 65, 645–652.
Bai J., Nakamura H., Kwon Y.W., Hattori I., Yamaguchi Y., Kim Y.C., et al. (2003) Critical roles of thioredoxin in nerve growth factor-mediated signal transduction and neurite out-growth in PC12 cells. J. Neurosci. 23, 503–509.
Montminy M.R., Sevarino K.A., Wagner J.A., Mandel G., and Goodman R.H. (1986) Identification of a cyclic-AMP-responsive element within the rat somatostatin gene. Proc. Natl. Acad. Sci. USA 83, 6682–6686.
Impey S., Obrietan K., Wong S.T., Poser S., Yano S., Wayman G., et al. (1998) Cross talk between ERK and PKA is required for Ca2+ stimulation of CREB-dependent transcription and ERK nuclear translocation. Neuron 21, 869–883.
Pan Z., Sampath D., Jackson G., Werrbach-Perez K., and Perez-Polo R. (1997) Nerve growth factor and oxidative stress in the nervous system. Adv. Exp. Med. Biol. 429, 173–193.
Ahn S., Olive M., Aggarwal S., Krylov D., Ginty D.D., and Vinson C. (1998) A dominant-negative inhibitor of CREB reveals that it is a general mediator of stimulus-dependent transcription of c-fos. Mol. Cell Biol. 18, 967–977.
Sheng M. and Greenberg M.E. (1990) The regulation and function of c-fos and other immediate early genes in the nervous system. Neuron 4, 477–485.
Chiarini L.B., Freitas F.G., Petrs-Silva H., and Linden R. (2000) Evidence that the bifunctional redox factor/AP endonuclease Ref-1 is an anti-apoptotic protein associated with differentiation in the developing retina. Cell Death Differ. 7, 272–281.
Hirota K., Matsui M., Murata M., Takashima Y., Cheng F.S., Itoh T., et al. (2000) Nucleoredoxin, glutaredoxin, and thioredoxin differentially regulate NF-kappaB, AP-1, and CREB activation in HEK293 cells. Biochem. Biophys. Res. Commun. 274, 177–182.
Hollowell J.P., Villadiego A., and Rich K.M. (1990) Sciatic nerve regeneration across gaps within silicone chambers: long-term effects of NGF and consideration of axonal branching. Exp. Neurol. 110, 45–51.
Kane D.J., Sarafian T.A., Anton R., Hahn H., Gralla E.B., Valentine J.S., et al. (1993) Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species. Science 262, 1274–1277.
Endoh M., Kunishita T., and Tabira T. (1993) Thioredoxin from activated macrophages as a trophic factor for central cholinergic neurons in vitro. Biochem. Biophys. Res. Commun. 192, 760–765.
Ishii K., Katayama M., Hori K., Yodoi J., and Nakanishi T. (1993) Effects of 2-mercaptoethanol on survival and differentiation of fetal mouse brain neurons cultured in vitro. Neurosci. Lett. 163, 159–162.
Davies A.M. (2003) Regulation of neuronal survival and death by extracellular signals during development. EMBO J. 22, 2537–2545.
Pallage V., Toniolo G., Will B., and Hefti F. (1986) Long-term effects of nerve growth factor and neural transplants on behavior of rats with medial septal lesions. Brain Res. 386, 197–208.
Kanamoto T., Mota M., Takeda K., Rubin L.L., Miyazono K., Ichijo H., et al. (2000) Role of apoptosis signal-regulating kinase in regulation of the c-Jun N-terminal kinase pathway and apoptosis in sympathetic neurons. Mol. Cell Biol. 20, 196–204.
Kummer J.L., Rao P.K., and Heidenreich K.A. (1997) Apoptosis induced by withdrawal of trophic factors is mediated by p38 mitogenactivated protein kinase. J. Biol. Chem. 272, 20,490–20,494.
Xia Z., Dickens M., Raingeaud J., Davis R.J., and Greenberg M.E. (1995) Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 270, 1326–1331.
Hashimoto S., Matsumoto K., Gon Y., Furuichi S., Maruoka S., Takeshita I., et al. (1999) Thioredoxin negatively regulates p38 MAP kinase activation and IL-6 production by tumor necrosis factor-alpha. Biochem. Biophys. Res. Commun. 258, 443–447.
Bruckner S.R., Perry G., and Estus S. (2003) 4-hydroxynonenal contributes to NGF withdrawal-induced neuronal apoptosis. J. Neurochem. 85, 999–1005.
Mitsui A., Hirakawa T., and Yodoi J. (1992) Reactive oxygen-reducing and protein-refolding activities of adult T cell leukemia-derived factor/human thioredoxin. Biochem. Biophys. Res. Commun. 186, 1220–1226.
Matsuda M., Masutani H., Nakamura H., Miyajima S., Yamauchi A., Yonehara S., et al. (1991) Protective activity of adult T cell leukemia-derived factor (ADF) against tumor necrosis factor-dependent cytotoxicity on U937 cells. J. Immunol. 147, 3837–3841.
Nakamura H., Matsuda M., Furuke K., Kitaoka Y., Iwata S., Toda K., et al. (1994) Adult T cell leukemia-derived factor/human thioredoxin protects endothelial F-2 cell injury caused by activated neutrophils or hydrogen peroxide. Immunol. Lett. 42, 75–80.
Kasuno K., Nakamura H., Ono T., Muso E., and Yodoi J. (2003) Protective role of thioredoxin, a redox regulating protein in renal ischemia/reperfusion injury. Kidney Int. 64, 1273–1282.
Hori K., Katayama M., Sato N., Ishii K., Waga S., and Yodoi J. (1994) Neuroprotection by glial cells through adult T cell leukemia-derived factor/human thioredoxin (ADF/TRX). Brain Res. 652, 304–310.
Ichimiya S., Davis J.G., O’Rourke D.M., Katsumata M., and Greene M.I. (1997) Murine thioredoxin peroxidase delays neuronal apoptosis and is expressed in areas of the brain most susceptible to hypoxic and ischemic injury. DNA Cell Biol. 16, 311–321.
Takagi Y., Mitsui A., Nishiyama A., Nozaki K., Sono H., Gon Y., et al. (1999) Overexpression of thioredoxin in transgenic mice attenuates focal ischemic brain damage. Proc. Natl. Acad. Sci. USA 96, 4131–4136.
Takagi Y., Hattori I., Nozaki K., Mitsui A., Ishikawa M., Hashimoto N., et al. (2000) Excitotoxic hippocampal injury is attenuated in thioredoxin transgenic mice. J. Cereb. Blood Flow Metab. 20, 829–833.
Tanito M., Nishiyama A., Tanaka T., Masutani H., Nakamura H., Yodoi J., et al. (2002) Change of redox status and modulation by thiol replenishment in retinal photooxidative damage. Invest. Ophthalmol. Vis. Sci. 43, 2392–2400.
Lovell M.A., Xie C., Gabbita S.P., and Markesbery W.R. (2000) Decreased thioredoxin and increased thioredoxin reductase levels in Alzheimer’s disease brain. Free Radic. Biol. Med. 28, 418–427.
Bai J., Nakamura H., Hattori I., Tanito M., and Yodoi J. (2002) Thioredoxin suppresses 1-methyl-4-phenylpyridinium-induced neurotoxicity in rat PC12 cells. Neurosci. Lett. 321, 81–84.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Masutani, H., Bai, J., Kim, YC. et al. Thioredoxin as a neurotrophic cofactor and an important regulator of neuroprotection. Mol Neurobiol 29, 229–242 (2004). https://doi.org/10.1385/MN:29:3:229
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1385/MN:29:3:229