Skip to main content
SpringerLink
Log in

Reactive Oxygen Species as Initiators and Mediators of Cellular Signaling Processes

  • Chapter
Studies on Experimental Toxicology and Pharmacology

Abstract

Reactive oxygen species (ROS) are both mediators and initiators of signaling processes in mammalian cells. Endogenous signaling cascades rely on the enzymatic formation of ROS to mediate transduction of the original signal, whereas many xenobiotics cause endogenous formation of ROS, which then trigger signaling cascades. Here, examples of endogenous ROS sources and of xenobiotic-derived ROS triggering signaling cascades are provided, followed by a discussion of how ROS can stimulate signaling processes. Finally, examples of ROS-dependent regulation of gene expression at transcriptional, epigenetic and posttranscriptional levels are provided.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Zheng M, Storz G (2000) Redox sensing by prokaryotic transcription factors. Biochem Pharmacol 59:1–6

    Article  CAS  PubMed  Google Scholar 

  2. Pomposiello PJ, Demple B (2001) Redox-operated genetic switches: the SoxR and OxyR transcription factors. Trends Biotechnol 19:109–114

    Article  CAS  PubMed  Google Scholar 

  3. Abate C, Patel L, Rauscher FJ 3rd, Curran T (1990) Redox regulation of fos and jun DNA-binding activity in vitro. Science 249:1157–1161

    Article  CAS  PubMed  Google Scholar 

  4. Schreck R, Rieber P, Baeuerle PA (1991) Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1. EMBO J 10:2247–2258

    PubMed Central  CAS  PubMed  Google Scholar 

  5. Babior BM (1984) The respiratory burst of phagocytes. J Clin Invest 73:599–601

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Katsuyama M, Matsuno K, Yabe-Nishimura C (2012) Physiological roles of NOX/NADPH oxidase, the superoxide-generating enzyme. J Clin Biochem Nutr 50:9–22

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Brown DI, Griendling KK (2009) Nox proteins in signal transduction. Free Radic Biol Med 47:1239–1253

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Jiang F, Zhang Y, Dusting GJ (2011) NADPH oxidase-mediated redox signaling: roles in cellular stress response, stress tolerance, and tissue repair. Pharmacol Rev 63:218–242

    Article  CAS  PubMed  Google Scholar 

  9. Marla SS, Lee J, Groves JT (1997) Peroxynitrite rapidly permeates phospholipid membranes. Proc Natl Acad Sci U S A 94:14243–14248

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Antunes F, Cadenas E (2000) Estimation of H2O2 gradients across biomembranes. FEBS Lett 475:121–126

    Article  CAS  PubMed  Google Scholar 

  11. Bienert GP, Chaumont F (2014) Aquaporin-facilitated transmembrane diffusion of hydrogen peroxide. Biochim Biophys Acta 1840:1596–1604

    Article  CAS  PubMed  Google Scholar 

  12. Miller EW, Dickinson BC, Chang CJ (2010) Aquaporin-3 mediates hydrogen peroxide uptake to regulate downstream intracellular signaling. Proc Natl Acad Sci U S A 107:15681–15686

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Vieceli Dalla Sega F, Zambonin L, Fiorentini D, Rizzo B, Caliceti C, Landi L, Hrelia S, Prata C (2014) Specific aquaporins facilitate Nox-produced hydrogen peroxide transport through plasma membrane in leukaemia cells. Biochim Biophys Acta 1843:806–814

    Article  CAS  PubMed  Google Scholar 

  14. Bienert GP, Moller AL, Kristiansen KA, Schulz A, Moller IM, Schjoerring JK, Jahn TP (2007) Specific aquaporins facilitate the diffusion of hydrogen peroxide across membranes. J Biol Chem 282:1183–1192

    Article  CAS  PubMed  Google Scholar 

  15. Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417:1–13

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  16. Bandy B, Davison AJ (1990) Mitochondrial mutations may increase oxidative stress: implications for carcinogenesis and aging? Free Radic Biol Med 8:523–539

    Article  CAS  PubMed  Google Scholar 

  17. Gruber J, Ng LF, Fong S, Wong YT, Koh SA, Chen CB, Shui G, Cheong WF, Schaffer S, Wenk MR, Halliwell B (2011) Mitochondrial changes in ageing Caenorhabditis elegans–what do we learn from superoxide dismutase knockouts? PLoS One 6, e19444

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Yun J, Finkel T (2014) Mitohormesis. Cell Metab 19:757–766

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Finkel T (2012) Signal transduction by mitochondrial oxidants. J Biol Chem 287:4434–4440

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Emerling BM, Weinberg F, Snyder C, Burgess Z, Mutlu GM, Viollet B, Budinger GR, Chandel NS (2009) Hypoxic activation of AMPK is dependent on mitochondrial ROS but independent of an increase in AMP/ATP ratio. Free Radic Biol Med 46:1386–1391

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Salminen A, Kaarniranta K (2012) AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Res Rev 11:230–241

    Article  CAS  PubMed  Google Scholar 

  22. Schmeisser S, Schmeisser K, Weimer S, Groth M, Priebe S, Fazius E, Kuhlow D, Pick D, Einax JW, Guthke R, Platzer M, Zarse K, Ristow M (2013) Mitochondrial hormesis links low-dose arsenite exposure to lifespan extension. Aging Cell 12:508–517

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. Ristow M, Schmeisser S (2011) Extending life span by increasing oxidative stress. Free Radic Biol Med 51:327–336

    Article  CAS  PubMed  Google Scholar 

  24. Ristow M, Schmeisser K (2014) Mitohormesis: promoting health and lifespan by increased levels of reactive oxygen species (ROS). Dose Response 12:288–341

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  25. Dugan LL, You YH, Ali SS, Diamond-Stanic M, Miyamoto S, Decleves AE, Andreyev A, Quach T, Ly S, Shekhtman G, Nguyen W, Chepetan A, Le TP, Wang L, Xu M, Paik KP, Fogo A, Viollet B, Murphy A, Brosius F, Naviaux RK, Sharma K (2013) AMPK dysregulation promotes diabetes-related reduction of superoxide and mitochondrial function. J Clin Invest 123:4888–4899

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Towler DA (2013) Mitochondrial ROS deficiency and diabetic complications: AMP[K]-lifying the adaptation to hyperglycemia. J Clin Invest 123:4573–4576

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Bae YS, Kang SW, Seo MS, Baines IC, Tekle E, Chock PB, Rhee SG (1997) Epidermal growth factor (EGF)-induced generation of hydrogen peroxide. Role in EGF receptor-mediated tyrosine phosphorylation. J Biol Chem 272:217–221

    Article  CAS  PubMed  Google Scholar 

  28. Deyulia GJ Jr, Carcamo JM (2005) EGF receptor-ligand interaction generates extracellular hydrogen peroxide that inhibits EGFR-associated protein tyrosine phosphatases. Biochem Biophys Res Commun 334:38–42

    Article  CAS  PubMed  Google Scholar 

  29. Sundaresan M, Yu ZX, Ferrans VJ, Irani K, Finkel T (1995) Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Science 270:296–299

    Article  CAS  PubMed  Google Scholar 

  30. Chen K, Kirber MT, Xiao H, Yang Y, Keaney JF Jr (2008) Regulation of ROS signal transduction by NADPH oxidase 4 localization. J Cell Biol 181:1129–1139

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  31. Mahadev K, Wu X, Zilbering A, Zhu L, Lawrence JT, Goldstein BJ (2001) Hydrogen peroxide generated during cellular insulin stimulation is integral to activation of the distal insulin signaling cascade in 3T3-L1 adipocytes. J Biol Chem 276:48662–48669

    Article  CAS  PubMed  Google Scholar 

  32. Mahadev K, Zilbering A, Zhu L, Goldstein BJ (2001) Insulin-stimulated hydrogen peroxide reversibly inhibits protein-tyrosine phosphatase 1b in vivo and enhances the early insulin action cascade. J Biol Chem 276:21938–21942

    Article  CAS  PubMed  Google Scholar 

  33. Meng TC, Buckley DA, Galic S, Tiganis T, Tonks NK (2004) Regulation of insulin signaling through reversible oxidation of the protein-tyrosine phosphatases TC45 and PTP1B. J Biol Chem 279:37716–37725

    Article  CAS  PubMed  Google Scholar 

  34. Mahadev K, Motoshima H, Wu X, Ruddy JM, Arnold RS, Cheng G, Lambeth JD, Goldstein BJ (2004) The NAD(P)H oxidase homolog Nox4 modulates insulin-stimulated generation of H2O2 and plays an integral role in insulin signal transduction. Mol Cell Biol 24:1844–1854

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  35. Lassegue B, San Martin A, Griendling KK (2012) Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system. Circ Res 110:1364–1390

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  36. Schröder K, Wandzioch K, Helmcke I, Brandes RP (2009) Nox4 acts as a switch between differentiation and proliferation in preadipocytes. Arterioscler Thromb Vasc Biol 29:239–245

    Article  PubMed  CAS  Google Scholar 

  37. Wancket LM, Frazier WJ, Liu Y (2012) Mitogen-activated protein kinase phosphatase (MKP)-1 in immunology, physiology, and disease. Life Sci 90:237–248

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  38. Seshiah PN, Weber DS, Rocic P, Valppu L, Taniyama Y, Griendling KK (2002) Angiotensin II stimulation of NAD(P)H oxidase activity: upstream mediators. Circ Res 91:406–413

    Article  CAS  PubMed  Google Scholar 

  39. Queisser N, Fazeli G, Schupp N (2010) Superoxide anion and hydrogen peroxide-induced signaling and damage in angiotensin II and aldosterone action. Biol Chem 391:1265–1279

    Article  CAS  PubMed  Google Scholar 

  40. Queisser N, Schupp N (2012) Aldosterone, oxidative stress, and NF-kappaB activation in hypertension-related cardiovascular and renal diseases. Free Radic Biol Med 53:314–327

    Article  CAS  PubMed  Google Scholar 

  41. Murry CE, Jennings RB, Reimer KA (1986) Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium. Circulation 74:1124–1136

    Article  CAS  PubMed  Google Scholar 

  42. Bell RM, Cave AC, Johar S, Hearse DJ, Shah AM, Shattock MJ (2005) Pivotal role of NOX-2-containing NADPH oxidase in early ischemic preconditioning. FASEB J 19:2037–2039

    CAS  PubMed  Google Scholar 

  43. Ostrakhovitch EA, Lordnejad MR, Schliess F, Sies H, Klotz LO (2002) Copper ions strongly activate the phosphoinositide-3-kinase/Akt pathway independent of the generation of reactive oxygen species. Arch Biochem Biophys 397:232–239

    Article  CAS  PubMed  Google Scholar 

  44. Walter PL, Kampkötter A, Eckers A, Barthel A, Schmoll D, Sies H, Klotz LO (2006) Modulation of FoxO signaling in human hepatoma cells by exposure to copper or zinc ions. Arch Biochem Biophys 454:107–113

    Article  CAS  PubMed  Google Scholar 

  45. Barthel A, Ostrakhovitch EA, Walter PL, Kampkötter A, Klotz LO (2007) Stimulation of phosphoinositide 3-kinase/Akt signaling by copper and zinc ions: mechanisms and consequences. Arch Biochem Biophys 463:175–182

    Article  CAS  PubMed  Google Scholar 

  46. Von Montfort C, Fernau NS, Beier JI, Sies H, Klotz LO (2006) Extracellular generation of hydrogen peroxide is responsible for activation of EGF receptor by ultraviolet A radiation. Free Radic Biol Med 41:1478–1487

    Article  CAS  Google Scholar 

  47. Bartholome A, Kampkötter A, Tanner S, Sies H, Klotz LO (2010) Epigallocatechin gallate-induced modulation of FoxO signaling in mammalian cells and C. elegans: FoxO stimulation is masked via PI3K/Akt activation by hydrogen peroxide formed in cell culture. Arch Biochem Biophys 501:58–64

    Article  CAS  PubMed  Google Scholar 

  48. Klaus V, Hartmann T, Gambini J, Graf P, Stahl W, Hartwig A, Klotz LO (2010) 1,4-Naphthoquinones as inducers of oxidative damage and stress signaling in HaCaT human keratinocytes. Arch Biochem Biophys 496:93–100

    Article  CAS  PubMed  Google Scholar 

  49. Vasquez-Vivar J, Augusto O (1992) Hydroxylated metabolites of the antimalarial drug primaquine. Oxidation and redox cycling. J Biol Chem 267:6848–6854

    CAS  PubMed  Google Scholar 

  50. Vasquez-Vivar J, Augusto O (1994) Oxidative activity of primaquine metabolites on rat erythrocytes in vitro and in vivo. Biochem Pharmacol 47:309–316

    Article  CAS  PubMed  Google Scholar 

  51. Winterbourn CC, Cowden WB, Sutton HC (1989) Auto-oxidation of dialuric acid, divicine and isouramil. Superoxide dependent and independent mechanisms. Biochem Pharmacol 38:611–618

    Article  CAS  PubMed  Google Scholar 

  52. Beier JI, Von Montfort C, Sies H, Klotz LO (2006) Activation of ErbB2 by 2-methyl-1,4-naphthoquinone (menadione) in human keratinocytes: role of EGFR and protein tyrosine phosphatases. FEBS Lett 580:1859–1864

    Article  CAS  PubMed  Google Scholar 

  53. Abdelmohsen K, Gerber PA, Von Montfort C, Sies H, Klotz LO (2003) Epidermal growth factor receptor is a common mediator of quinone-induced signaling leading to phosphorylation of connexin-43 – Role of glutathione and tyrosine phosphatases. J Biol Chem 278:38360–38367

    Article  CAS  PubMed  Google Scholar 

  54. Abdelmohsen K, Patak P, Von Montfort C, Melchheier I, Sies H, Klotz LO (2004) Signaling effects of menadione: from tyrosine phosphatase inactivation to connexin phosphorylation. Methods Enzymol 378:258–272

    Article  CAS  PubMed  Google Scholar 

  55. Von Montfort C, Sharov VS, Metzger S, Schöneich C, Sies H, Klotz LO (2006) Singlet oxygen inactivates protein tyrosine phosphatase-1B by oxidation of the active site cysteine. Biol Chem 387:1399–1404

    Google Scholar 

  56. Bigelow DJ, Squier TC (2011) Thioredoxin-dependent redox regulation of cellular signaling and stress response through reversible oxidation of methionines. Mol Biosyst 7:2101–2109

    Article  CAS  PubMed  Google Scholar 

  57. Wang X, Mccullough KD, Franke TF, Holbrook NJ (2000) Epidermal growth factor receptor-dependent Akt activation by oxidative stress enhances cell survival. J Biol Chem 275:14624–14631

    Article  CAS  PubMed  Google Scholar 

  58. Klotz LO, Schieke SM, Sies H, Holbrook NJ (2000) Peroxynitrite activates the phosphoinositide 3-kinase/Akt pathway in human skin primary fibroblasts. Biochem J 352(Pt 1):219–225

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  59. Klotz LO, Schroeder P, Sies H (2002) Peroxynitrite signaling: receptor tyrosine kinases and activation of stress-responsive pathways. Free Radic Biol Med 33:737–743

    Article  CAS  PubMed  Google Scholar 

  60. Klotz LO, Patak P, Ale-Agha N, Buchczyk DP, Abdelmohsen K, Gerber PA, Von Montfort C, Sies H (2002) 2-Methyl-1,4-naphthoquinone, vitamin K(3), decreases gap-junctional intercellular communication via activation of the epidermal growth factor receptor/extracellular signal-regulated kinase cascade. Cancer Res 62:4922–4928

    CAS  PubMed  Google Scholar 

  61. Knebel A, Rahmsdorf HJ, Ullrich A, Herrlich P (1996) Dephosphorylation of receptor tyrosine kinases as target of regulation by radiation, oxidants or alkylating agents. EMBO J 15:5314–5325

    PubMed Central  CAS  PubMed  Google Scholar 

  62. Kolmodin K, Aqvist J (2001) The catalytic mechanism of protein tyrosine phosphatases revisited. FEBS Lett 498:208–213

    Article  CAS  PubMed  Google Scholar 

  63. Östman A, Frijhoff J, Sandin A, Böhmer FD (2011) Regulation of protein tyrosine phosphatases by reversible oxidation. J Biochem 150:345–356

    Article  PubMed  CAS  Google Scholar 

  64. Salmeen A, Andersen JN, Myers MP, Meng TC, Hinks JA, Tonks NK, Barford D (2003) Redox regulation of protein tyrosine phosphatase 1B involves a sulphenyl-amide intermediate. Nature 423:769–773

    Article  CAS  PubMed  Google Scholar 

  65. Van Montfort RL, Congreve M, Tisi D, Carr R, Jhoti H (2003) Oxidation state of the active-site cysteine in protein tyrosine phosphatase 1B. Nature 423:773–777

    Article  PubMed  CAS  Google Scholar 

  66. Takakura K, Beckman JS, Macmillan-Crow LA, Crow JP (1999) Rapid and irreversible inactivation of protein tyrosine phosphatases PTP1B, CD45, and LAR by peroxynitrite. Arch Biochem Biophys 369:197–207

    Article  CAS  PubMed  Google Scholar 

  67. Iwamoto N, Sumi D, Ishii T, Uchida K, Cho AK, Froines JR, Kumagai Y (2007) Chemical knockdown of protein-tyrosine phosphatase 1B by 1,2-naphthoquinone through covalent modification causes persistent transactivation of epidermal growth factor receptor. J Biol Chem 282:33396–33404

    Article  CAS  PubMed  Google Scholar 

  68. Denu JM, Tanner KG (1998) Specific and reversible inactivation of protein tyrosine phosphatases by hydrogen peroxide: evidence for a sulfenic acid intermediate and implications for redox regulation. Biochemistry 37:5633–5642

    Article  CAS  PubMed  Google Scholar 

  69. Jeon TJ, Chien PN, Chun HJ, Ryu SE (2013) Structure of the catalytic domain of protein tyrosine phosphatase sigma in the sulfenic acid form. Mol Cells 36:55–61

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  70. Savitsky PA, Finkel T (2002) Redox regulation of Cdc25C. J Biol Chem 277:20535–20540

    Article  CAS  PubMed  Google Scholar 

  71. Lee SR, Yang KS, Kwon J, Lee C, Jeong W, Rhee SG (2002) Reversible inactivation of the tumor suppressor PTEN by H2O2. J Biol Chem 277:20336–20342

    Article  CAS  PubMed  Google Scholar 

  72. Arner ES, Holmgren A (2000) Physiological functions of thioredoxin and thioredoxin reductase. Eur J Biochem 267:6102–6109

    Article  CAS  PubMed  Google Scholar 

  73. Ray PD, Huang BW, Tsuji Y (2012) Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell Signal 24:981–990

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  74. Corcoran A, Cotter TG (2013) Redox regulation of protein kinases. FEBS J 280:1944–1965

    Article  CAS  PubMed  Google Scholar 

  75. Uchida K (2000) Role of reactive aldehyde in cardiovascular diseases. Free Radic Biol Med 28:1685–1696

    Article  CAS  PubMed  Google Scholar 

  76. Shearn CT, Smathers RL, Stewart BJ, Fritz KS, Galligan JJ, Hail N Jr, Petersen DR (2011) Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibition by 4-hydroxynonenal leads to increased Akt activation in hepatocytes. Mol Pharmacol 79:941–952

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  77. Kumagai T, Nakamura Y, Osawa T, Uchida K (2002) Role of p38 mitogen-activated protein kinase in the 4-hydroxy-2-nonenal-induced cyclooxygenase-2 expression. Arch Biochem Biophys 397:240–245

    Article  CAS  PubMed  Google Scholar 

  78. Chojkier M, Houglum K, Solis-Herruzo J, Brenner DA (1989) Stimulation of collagen gene expression by ascorbic acid in cultured human fibroblasts. A role for lipid peroxidation? J Biol Chem 264:16957–16962

    CAS  PubMed  Google Scholar 

  79. Garcia-Ruiz I, De La Torre P, Diaz T, Esteban E, Fernandez I, Munoz-Yague T, Solis-Herruzo JA (2002) Sp1 and Sp3 transcription factors mediate malondialdehyde-induced collagen alpha 1(I) gene expression in cultured hepatic stellate cells. J Biol Chem 277:30551–30558

    Article  CAS  PubMed  Google Scholar 

  80. Ott C, Jacobs K, Haucke E, Navarrete Santos A, Grune T, Simm A (2014) Role of advanced glycation end products in cellular signaling. Redox Biol 2:411–429

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  81. Klatt P, Lamas S (2000) Regulation of protein function by S-glutathiolation in response to oxidative and nitrosative stress. Eur J Biochem 267:4928–4944

    Article  CAS  PubMed  Google Scholar 

  82. Jacob C, Giles GI, Giles NM, Sies H (2003) Sulfur and selenium: the role of oxidation state in protein structure and function. Angew Chem Int Ed Engl 42:4742–4758

    Article  CAS  PubMed  Google Scholar 

  83. Jacob C (2011) Redox signalling via the cellular thiolstat. Biochem Soc Trans 39:1247–1253

    Article  CAS  PubMed  Google Scholar 

  84. Ernster L (1987) DT Diaphorase: a historical review. Chem Scr 27A:1–13

    CAS  Google Scholar 

  85. Dinkova-Kostova AT, Talalay P (2010) NAD(P)H:quinone acceptor oxidoreductase 1 (NQO1), a multifunctional antioxidant enzyme and exceptionally versatile cytoprotector. Arch Biochem Biophys 501:116–123

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  86. Li Y, Jaiswal AK (1992) Regulation of human NAD(P)H:quinone oxidoreductase gene. Role of AP1 binding site contained within human antioxidant response element. J Biol Chem 267:15097–15104

    CAS  PubMed  Google Scholar 

  87. Venugopal R, Jaiswal AK (1996) Nrf1 and Nrf2 positively and c-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD(P)H:quinone oxidoreductase1 gene. Proc Natl Acad Sci U S A 93:14960–14965

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  88. Kansanen E, Kuosmanen SM, Leinonen H, Levonen AL (2013) The Keap1-Nrf2 pathway: Mechanisms of activation and dysregulation in cancer. Redox Biol 1:45–49

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  89. Kops GJ, Dansen TB, Polderman PE, Saarloos I, Wirtz KW, Coffer PJ, Huang TT, Bos JL, Medema RH, Burgering BM (2002) Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress. Nature 419:316–321

    Article  CAS  PubMed  Google Scholar 

  90. Speckmann B, Walter PL, Alili L, Reinehr R, Sies H, Klotz LO, Steinbrenner H (2008) Selenoprotein P expression is controlled through interaction of the coactivator PGC-1alpha with FoxO1a and hepatocyte nuclear factor 4alpha transcription factors. Hepatology 48:1998–2006

    Article  CAS  PubMed  Google Scholar 

  91. Walter PL, Steinbrenner H, Barthel A, Klotz LO (2008) Stimulation of selenoprotein P promoter activity in hepatoma cells by FoxO1a transcription factor. Biochem Biophys Res Commun 365:316–321

    Article  CAS  PubMed  Google Scholar 

  92. Leyendecker M, Korsten P, Reinehr R, Speckmann B, Schmoll D, Scherbaum WA, Bornstein SR, Barthel A, Klotz LO (2011) Ceruloplasmin expression in rat liver cells is attenuated by insulin: role of FoxO transcription factors. Horm Metab Res 43:268–274

    Article  CAS  PubMed  Google Scholar 

  93. Monsalve M, Olmos Y (2011) The complex biology of FOXO. Curr Drug Targets 12:1322–1350

    Article  CAS  PubMed  Google Scholar 

  94. Barthel A, Klotz LO (2005) Phosphoinositide 3-kinase signaling in the cellular response to oxidative stress. Biol Chem 386:207–216

    Article  CAS  PubMed  Google Scholar 

  95. Hamann I, Petroll K, Hou X, Anwar-Mohamed A, El-Kadi AO, Klotz LO (2014) Acute and long-term effects of arsenite in HepG2 cells: modulation of insulin signaling. Biometals 27:317–332

    Article  CAS  PubMed  Google Scholar 

  96. Hamann I, Klotz LO (2013) Arsenite-induced stress signaling: Modulation of the phosphoinositide 3′-kinase/Akt/FoxO signaling cascade. Redox Biol 1:104–109

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  97. Dansen TB, Smits LM, Van Triest MH, De Keizer PL, Van Leenen D, Koerkamp MG, Szypowska A, Meppelink A, Brenkman AB, Yodoi J, Holstege FC, Burgering BM (2009) Redox-sensitive cysteines bridge p300/CBP-mediated acetylation and FoxO4 activity. Nat Chem Biol 5:664–672

    Article  CAS  PubMed  Google Scholar 

  98. Van Der Vos KE, Coffer PJ (2008) FOXO-binding partners: it takes two to tango. Oncogene 27:2289–2299

    Article  PubMed  CAS  Google Scholar 

  99. Kodama S, Koike C, Negishi M, Yamamoto Y (2004) Nuclear receptors CAR and PXR cross talk with FOXO1 to regulate genes that encode drug-metabolizing and gluconeogenic enzymes. Mol Cell Biol 24:7931–7940

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  100. Eckers A, Sauerbier E, Anwar-Mohamed A, Hamann I, Esser C, Schroeder P, El-Kadi AO, Klotz LO (2011) Detection of a functional xenobiotic response element in a widely employed FoxO-responsive reporter construct. Arch Biochem Biophys 516:138–145

    Article  CAS  PubMed  Google Scholar 

  101. Kang KA, Zhang R, Kim GY, Bae SC, Hyun JW (2012) Epigenetic changes induced by oxidative stress in colorectal cancer cells: methylation of tumor suppressor RUNX3. Tumour Biol 33:403–412

    Article  CAS  PubMed  Google Scholar 

  102. Escobar J, Pereda J, Lopez-Rodas G, Sastre J (2012) Redox signaling and histone acetylation in acute pancreatitis. Free Radic Biol Med 52:819–837

    Article  CAS  PubMed  Google Scholar 

  103. Wang W, Furneaux H, Cheng H, Caldwell MC, Hutter D, Liu Y, Holbrook N, Gorospe M (2000) HuR regulates p21 mRNA stabilization by UV light. Mol Cell Biol 20:760–769

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  104. Tran H, Maurer F, Nagamine Y (2003) Stabilization of urokinase and urokinase receptor mRNAs by HuR is linked to its cytoplasmic accumulation induced by activated mitogen-activated protein kinase-activated protein kinase 2. Mol Cell Biol 23:7177–7188

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  105. Fernau NS, Fugmann D, Leyendecker M, Reimann K, Grether-Beck S, Galban S, Ale-Agha N, Krutmann J, Klotz LO (2010) Role of HuR and p38MAPK in ultraviolet B-induced post-transcriptional regulation of COX-2 expression in the human keratinocyte cell line HaCaT. J Biol Chem 285:3896–3904

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  106. Bhattacharyya SN, Habermacher R, Martine U, Closs EI, Filipowicz W (2006) Relief of microRNA-mediated translational repression in human cells subjected to stress. Cell 125:1111–1124

    Article  CAS  PubMed  Google Scholar 

  107. Song IS, Tatebe S, Dai W, Kuo MT (2005) Delayed mechanism for induction of gamma-glutamylcysteine synthetase heavy subunit mRNA stability by oxidative stress involving p38 mitogen-activated protein kinase signaling. J Biol Chem 280:28230–28240

    Article  CAS  PubMed  Google Scholar 

  108. Abdelmohsen K, Kuwano Y, Kim HH, Gorospe M (2008) Posttranscriptional gene regulation by RNA-binding proteins during oxidative stress: implications for cellular senescence. Biol Chem 389:243–255

    Article  CAS  PubMed  Google Scholar 

  109. Subbaramaiah K, Marmo TP, Dixon DA, Dannenberg AJ (2003) Regulation of cyclooxgenase-2 mRNA stability by taxanes: evidence for involvement of p38, MAPKAPK-2, and HuR. J Biol Chem 278:37637–37647

    Article  CAS  PubMed  Google Scholar 

  110. Lafarga V, Cuadrado A, Lopez De Silanes I, Bengoechea R, Fernandez-Capetillo O, Nebreda AR (2009) p38 Mitogen-activated protein kinase- and HuR-dependent stabilization of p21(Cip1) mRNA mediates the G(1)/S checkpoint. Mol Cell Biol 29:4341–4351

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  111. Masuda K, Abdelmohsen K, Gorospe M (2009) RNA-binding proteins implicated in the hypoxic response. J Cell Mol Med 13:2759–2769

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  112. King FW, Shtivelman E (2004) Inhibition of nuclear import by the proapoptotic protein CC3. Mol Cell Biol 24:7091–7101

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  113. Zhao J, Chen J, Lu B, Dong L, Wang H, Bi C, Wu G, Guo H, Wu M, Guo Y (2008) TIP30 induces apoptosis under oxidative stress through stabilization of p53 messenger RNA in human hepatocellular carcinoma. Cancer Res 68:4133–4141

    Article  CAS  PubMed  Google Scholar 

  114. Benoit RM, Meisner NC, Kallen J, Graff P, Hemmig R, Cebe R, Ostermeier C, Widmer H, Auer M (2010) The x-ray crystal structure of the first RNA recognition motif and site-directed mutagenesis suggest a possible HuR redox sensing mechanism. J Mol Biol 397:1231–1244

    Article  CAS  PubMed  Google Scholar 

  115. Krol J, Loedige I, Filipowicz W (2010) The widespread regulation of microRNA biogenesis, function and decay. Nat Rev Genet 11:597–610

    CAS  PubMed  Google Scholar 

  116. Magenta A, Greco S, Gaetano C, Martelli F (2013) Oxidative stress and microRNAs in vascular diseases. Int J Mol Sci 14:17319–17346

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  117. Mori MA, Raghavan P, Thomou T, Boucher J, Robida-Stubbs S, Macotela Y, Russell SJ, Kirkland JL, Blackwell TK, Kahn CR (2012) Role of microRNA processing in adipose tissue in stress defense and longevity. Cell Metab 16:336–347

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  118. Kundu P, Fabian MR, Sonenberg N, Bhattacharyya SN, Filipowicz W (2012) HuR protein attenuates miRNA-mediated repression by promoting miRISC dissociation from the target RNA. Nucleic Acids Res 40:5088–5100

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  119. Klotz LO (2014) Oxidative stress, antioxidants, and chemoprevention: on the role of oxidant-induced signaling in cellular adaptation. In: Jacob C, Kirsch G, Slusarenko AJ, Winyard PG, Burkholz T (eds) Recent advances in redox active plant and microbial products. Springer, Dordrecht, pp 119–146

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nutrigenomics, Institute of Nutrition, Friedrich Schiller University Jena, Dornburger Str. 29, 07743, Jena, Thüringen, Germany

    Lars-Oliver Klotz

Authors
  1. Lars-Oliver Klotz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Lars-Oliver Klotz .

Editor information

Editors and Affiliations

  1. Center for Environmental & Human Toxicology, University of Florida, Gainesville, Florida, USA

    Stephen M. Roberts

  2. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada

    James P. Kehrer

  3. Department of Nutrigenomics, Institute of Nutrition, Friedrich Schiller University Jena, Jena, Thüringen, Germany

    Lars-Oliver Klotz

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Klotz, LO. (2015). Reactive Oxygen Species as Initiators and Mediators of Cellular Signaling Processes. In: Roberts, S., Kehrer, J., Klotz, LO. (eds) Studies on Experimental Toxicology and Pharmacology. Oxidative Stress in Applied Basic Research and Clinical Practice. Humana Press, Cham. https://doi.org/10.1007/978-3-319-19096-9_8

Download citation

Publish with us

Policies and ethics

Search

Navigation