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The Molecular Regulation and Functional Roles of NOX5

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NADPH Oxidases

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1982))

Abstract

NOX (NADPH oxidases) are a family of NADPH-dependent transmembrane enzymes that synthesize superoxide and other reactive oxygen species. There are seven isoforms (NOX1–5 and DUOX1–2) which derive from a common ancestral NOX. NOX enzymes are distinguished by different modes of activation, the types of ROS that are produced, the cell types where they are expressed, and distinct functional roles. NOX5 was one of the earliest eukaryotic Nox enzymes to evolve and ironically the last isoform to be discovered in humans. In the time since its discovery, our knowledge of the regulation of NOX5 has expanded tremendously, and we now have a more comprehensive understanding of the molecular mechanisms underlying NOX5-dependent ROS production. In contrast, the cell types where NOX5 is robustly expressed and its functional significance in health and disease remain an underdeveloped area. The goal of this chapter is to provide an up-to-date overview of the mechanisms regulating NOX5 function and its importance in human physiology and pathophysiology.

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References

  1. Banfi B, Molnar G, Maturana A, Steger K, Hegedus B, Demaurex N, Krause KH (2001) A Ca(2+)-activated NADPH oxidase in testis, spleen, and lymph nodes. J Biol Chem 276(40):37594–37601

    Article  CAS  PubMed  Google Scholar 

  2. Cheng G, Cao Z, Xu X, van Meir EG, Lambeth JD (2001) Homologs of gp91phox: cloning and tissue expression of Nox3, Nox4, and Nox5. Gene 269(1–2):131–140

    Article  CAS  PubMed  Google Scholar 

  3. Jackson HM, Kawahara T, Nisimoto Y, Smith SM, Lambeth JD (2010) Nox4 B-loop creates an interface between the transmembrane and dehydrogenase domains. J Biol Chem 285(14):10281–10290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Magnani F, Nenci S, Millana Fananas E, Ceccon M, Romero E, Fraaije MW, Mattevi A (2017) Crystal structures and atomic model of NADPH oxidase. Proc Natl Acad Sci U S A 114(26):6764–6769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Kawahara T, Jackson HM, Smith SM, Simpson PD, Lambeth JD (2011) Nox5 forms a functional oligomer mediated by self-association of its dehydrogenase domain. Biochemistry 50(12):2013–2025

    Article  CAS  PubMed  Google Scholar 

  6. von Lohneysen K, Noack D, Wood MR, Friedman JS, Knaus UG (2010) Structural insights into Nox4 and Nox2: motifs involved in function and cellular localization. Mol Cell Biol 30(4):961–975

    Article  CAS  Google Scholar 

  7. Rigutto S, Hoste C, Grasberger H, Milenkovic M, Communi D, Dumont JE, Corvilain B, Miot F, De Deken X (2009) Activation of dual oxidases Duox1 and Duox2: differential regulation mediated by camp-dependent protein kinase and protein kinase C-dependent phosphorylation. J Biol Chem 284(11):6725–6734

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Banfi B, Tirone F, Durussel I, Knisz J, Moskwa P, Molnar GZ, Krause KH, Cox JA (2004) Mechanism of Ca2+ activation of the NADPH oxidase 5 (NOX5). J Biol Chem 279(18):18583–18591

    Article  CAS  PubMed  Google Scholar 

  9. Jagnandan D, Church JE, Banfi B, Stuehr DJ, Marrero MB, Fulton DJ (2007) Novel mechanism of activation of NADPH oxidase 5. calcium sensitization via phosphorylation. J Biol Chem 282(9):6494–6507

    Article  CAS  PubMed  Google Scholar 

  10. Wei CC, Reynolds N, Palka C, Wetherell K, Boyle T, Yang YP, Wang ZQ, Stuehr DJ (2012) Characterization of the 1st and 2nd EF-hands of NADPH oxidase 5 by fluorescence, isothermal titration calorimetry, and circular dichroism. Chem Cent J 6(1):29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Tirone F, Radu L, Craescu CT, Cox JA (2010) Identification of the binding site for the regulatory calcium-binding domain in the catalytic domain of NOX5. Biochemistry 49(4):761–771

    Article  CAS  PubMed  Google Scholar 

  12. Serrander L, Jaquet V, Bedard K, Plastre O, Hartley O, Arnaudeau S, Demaurex N, Schlegel W, Krause KH (2007) NOX5 is expressed at the plasma membrane and generates superoxide in response to protein kinase C activation. Biochimie 89(9):1159–1167

    Article  CAS  PubMed  Google Scholar 

  13. Chen F, Yu Y, Haigh S, Johnson J, Lucas R, Stepp DW, Fulton DJ (2014) Regulation of NADPH oxidase 5 by protein kinase C isoforms. PLoS One 9(2):e88405

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Pandey D, Fulton DJ (2011) Molecular regulation of NADPH oxidase 5 via the MAPK pathway. Am J Physiol Heart Circ Physiol 300(4):H1336–H1344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Montezano AC, Burger D, Paravicini TM, Chignalia AZ, Yusuf H, Almasri M, He Y, Callera GE, He G, Krause KH, Lambeth D, Quinn MT, Touyz RM (2010) Nicotinamide adenine dinucleotide phosphate reduced oxidase 5 (Nox5) regulation by angiotensin II and endothelin-1 is mediated via calcium/calmodulin-dependent, rac-1-independent pathways in human endothelial cells. Circ Res 106(8):1363–1373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Pandey D, Gratton JP, Rafikov R, Black SM, Fulton DJ (2011) Calcium/calmodulin-dependent kinase II mediates the phosphorylation and activation of NADPH oxidase 5. Mol Pharmacol 80(3):407–415

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Holterman CE, Thibodeau JF, Towaij C, Gutsol A, Montezano AC, Parks RJ, Cooper ME, Touyz RM, Kennedy CR (2014) Nephropathy and elevated BP in mice with podocyte-specific NADPH oxidase 5 expression. J Am Soc Nephrol 25(4):784–797

    Article  CAS  PubMed  Google Scholar 

  18. El Jamali A, Valente AJ, Lechleiter JD, Gamez MJ, Pearson DW, Nauseef WM, Clark RA (2008) Novel redox-dependent regulation of NOX5 by the tyrosine kinase c-Abl. Free Radic Biol Med 44(5):868–881

    Article  PubMed  CAS  Google Scholar 

  19. Dho SH, Kim JY, Kwon ES, Lim JC, Park SS, Kwon KS (2015) NOX5-L can stimulate proliferation and apoptosis depending on its levels and cellular context, determining cancer cell susceptibility to cisplatin. Oncotarget 6(36):39235–39246

    Article  PubMed  PubMed Central  Google Scholar 

  20. Musset B, Clark RA, DeCoursey TE, Petheo GL, Geiszt M, Chen Y, Cornell JE, Eddy CA, Brzyski RG, El Jamali A (2012) NOX5 in human spermatozoa: expression, function, and regulation. J Biol Chem 287(12):9376–9388

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87(1):245–313

    Article  CAS  PubMed  Google Scholar 

  22. BelAiba RS, Djordjevic T, Petry A, Diemer K, Bonello S, Banfi B, Hess J, Pogrebniak A, Bickel C, Gorlach A (2007) NOX5 variants are functionally active in endothelial cells. Free Radic Biol Med 42(4):446–459

    Article  CAS  PubMed  Google Scholar 

  23. Prior KK, Leisegang MS, Josipovic I, Lowe O, Shah AM, Weissmann N, Schroder K, Brandes RP (2016) CRISPR/Cas9-mediated knockout of p22phox leads to loss of Nox1 and Nox4, but not Nox5 activity. Redox Biol 9:287–295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Tirone F, Cox JA (2007) NADPH oxidase 5 (NOX5) interacts with and is regulated by calmodulin. FEBS Lett 581(6):1202–1208

    Article  CAS  PubMed  Google Scholar 

  25. Fridolfsson HN, Roth DM, Insel PA, Patel HH (2014) Regulation of intracellular signaling and function by caveolin. FASEB J 28(9):3823–3831

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Chen F, Barman S, Yu Y, Haigh S, Wang Y, Dou H, Bagi Z, Han W, Su Y, Fulton DJ (2014) Caveolin-1 is a negative regulator of NADPH oxidase-derived reactive oxygen species. Free Radic Biol Med 73:201–213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Hu G, Ye RD, Dinauer MC, Malik AB, Minshall RD (2008) Neutrophil caveolin-1 expression contributes to mechanism of lung inflammation and injury. Am J Physiol Lung Cell Mol Physiol 294(2):L178–L186

    Article  CAS  PubMed  Google Scholar 

  28. Lobysheva I, Rath G, Sekkali B, Bouzin C, Feron O, Gallez B, Dessy C, Balligand JL (2011) Moderate caveolin-1 downregulation prevents NADPH oxidase-dependent endothelial nitric oxide synthase uncoupling by angiotensin II in endothelial cells. Arterioscler Thromb Vasc Biol 31(9):2098–2105

    Article  CAS  PubMed  Google Scholar 

  29. Garcia-Cardena G, Oh P, Liu J, Schnitzer JE, Sessa WC (1996) Targeting of nitric oxide synthase to endothelial cell caveolae via palmitoylation: implications for nitric oxide signaling. Proc Natl Acad Sci U S A 93(13):6448–6453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Fulton D, Babbitt R, Zoellner S, Fontana J, Acevedo L, McCabe TJ, Iwakiri Y, Sessa WC (2004) Targeting of endothelial nitric-oxide synthase to the cytoplasmic face of the Golgi complex or plasma membrane regulates Akt- versus calcium-dependent mechanisms for nitric oxide release. J Biol Chem 279(29):30349–30357

    Article  CAS  PubMed  Google Scholar 

  31. Pavlides S, Tsirigos A, Vera I, Flomenberg N, Frank PG, Casimiro MC, Wang C, Fortina P, Addya S, Pestell RG, Martinez-Outschoorn UE, Sotgia F, Lisanti MP (2010) Loss of stromal caveolin-1 leads to oxidative stress, mimics hypoxia and drives inflammation in the tumor microenvironment, conferring the “reverse Warburg effect”: a transcriptional informatics analysis with validation. Cell Cycle 9(11):2201–2219

    Article  CAS  PubMed  Google Scholar 

  32. Karuppiah K, Druhan LJ, Chen CA, Smith T, Zweier JL, Sessa WC, Cardounel AJ (2011) Suppression of eNOS-derived superoxide by caveolin-1: a biopterin-dependent mechanism. Am J Physiol Heart Circ Physiol 301(3):H903–H911

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Zhao YY, Zhao YD, Mirza MK, Huang JH, Potula HH, Vogel SM, Brovkovych V, Yuan JX, Wharton J, Malik AB (2009) Persistent eNOS activation secondary to caveolin-1 deficiency induces pulmonary hypertension in mice and humans through PKG nitration. J Clin Invest 119(7):2009–2018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Basset O, Deffert C, Foti M, Bedard K, Jaquet V, Ogier-Denis E, Krause KH (2009) NADPH oxidase 1 deficiency alters caveolin phosphorylation and angiotensin II-receptor localization in vascular smooth muscle. Antioxid Redox Signal 11(10):2371–2384

    Article  CAS  PubMed  Google Scholar 

  35. Chen F, Pandey D, Chadli A, Catravas JD, Chen T, Fulton DJ (2011) Hsp90 regulates NADPH oxidase activity and is necessary for superoxide but not hydrogen peroxide production. Antioxid Redox Signal 14(11):2107–2119

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Chen F, Yu Y, Qian J, Wang Y, Cheng B, Dimitropoulou C, Patel V, Chadli A, Rudic RD, Stepp DW, Catravas JD, Fulton DJ (2012) Opposing actions of heat shock protein 90 and 70 regulate nicotinamide adenine dinucleotide phosphate oxidase stability and reactive oxygen species production. Arterioscler Thromb Vasc Biol 32(12):2989–2999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Madrigal-Matute J, Fernandez-Garcia CE, Gomez-Guerrero C, Lopez-Franco O, Munoz-Garcia B, Egido J, Blanco-Colio LM, Martin-Ventura JL (2012) HSP90 inhibition by 17-DMAG attenuates oxidative stress in experimental atherosclerosis. Cardiovasc Res 95(1):116–123

    Article  CAS  PubMed  Google Scholar 

  38. Chen F, Haigh S, Yu Y, Benson T, Wang Y, Li X, Dou H, Bagi Z, Verin AD, Stepp DW, Csanyi G, Chadli A, Weintraub NL, Smith SM, Fulton DJ (2015) Nox5 stability and superoxide production is regulated by C-terminal binding of Hsp90 and CO-chaperones. Free Radic Biol Med 89:793–805

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Takac I, Schroder K, Zhang L, Lardy B, Anilkumar N, Lambeth JD, Shah AM, Morel F, Brandes RP (2011) The E-loop is involved in hydrogen peroxide formation by the NADPH oxidase Nox4. J Biol Chem 286(15):13304–13313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Ueyama T, Sakuma M, Ninoyu Y, Hamada T, Dupuy C, Geiszt M, Leto TL, Saito N (2015) The extracellular A-loop of dual oxidases affects the specificity of reactive oxygen species release. J Biol Chem 290(10):6495–6506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Calderwood SK, Neckers L (2016) Hsp90 in cancer: transcriptional roles in the nucleus. Adv Cancer Res 129:89–106

    Article  CAS  PubMed  Google Scholar 

  42. Thangjam GS, Birmpas C, Barabutis N, Gregory BW, Clemens MA, Newton JR, Fulton D, Catravas JD (2016) Hsp90 inhibition suppresses NF-kappaB transcriptional activation via Sirt-2 in human lung microvascular endothelial cells. Am J Physiol Lung Cell Mol Physiol 310(10):L964–L974

    Article  PubMed  PubMed Central  Google Scholar 

  43. Kawahara T, Lambeth JD (2008) Phosphatidylinositol (4,5)-bisphosphate modulates Nox5 localization via an N-terminal polybasic region. Mol Biol Cell 19(10):4020–4031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Brar SS, Corbin Z, Kennedy TP, Hemendinger R, Thornton L, Bommarius B, Arnold RS, Whorton AR, Sturrock AB, Huecksteadt TP, Quinn MT, Krenitsky K, Ardie KG, Lambeth JD, Hoidal JR (2003) NOX5 NAD(P)H oxidase regulates growth and apoptosis in DU 145 prostate cancer cells. Am J Physiol Cell Physiol 285(2):C353–C369

    Article  CAS  PubMed  Google Scholar 

  45. Ambasta RK, Kumar P, Griendling KK, Schmidt H, Busse R, Brandes RP (2004) Direct interaction of the novel nox proteins with p22phox is required for the formation of a functionally active NADPH oxidase. J Biol Chem 279(44):45935–45941

    Article  CAS  PubMed  Google Scholar 

  46. Bayraktutan U, Blayney L, Shah AM (2000) Molecular characterization and localization of the NAD(P)H oxidase components gp91-phox and p22-phox in endothelial cells. Arterioscler Thromb Vasc Biol 20(8):1903–1911

    Article  CAS  PubMed  Google Scholar 

  47. Van Buul JD, Fernandez-Borja M, Anthony EC, Hordijk PL (2005) Expression and localization of NOX2 and NOX4 in primary human endothelial cells. Antioxid Redox Signal 7(3–4):308–317

    Article  PubMed  Google Scholar 

  48. 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(7):1129–1139

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kiyohara T, Miyano K, Kamakura S, Hayase J, Chishiki K, Kohda A, Sumimoto H (2018) Differential cell surface recruitment of the superoxide-producing NADPH oxidases Nox1, Nox2 and Nox5: the role of the small GTPase Sar1. Genes Cells 23(6):480–493

    Article  CAS  PubMed  Google Scholar 

  50. Gryglewski RJ, Palmer RM, Moncada S (1986) Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature 320(6061):454–456

    Article  CAS  PubMed  Google Scholar 

  51. Selemidis S, Dusting GJ, Peshavariya H, Kemp-Harper BK, Drummond GR (2007) Nitric oxide suppresses NADPH oxidase-dependent superoxide production by S-nitrosylation in human endothelial cells. Cardiovasc Res 75(2):349–358

    Article  CAS  PubMed  Google Scholar 

  52. Qian J, Chen F, Kovalenkov Y, Pandey D, Moseley MA, Foster MW, Black SM, Venema RC, Stepp DW, Fulton DJ (2012) Nitric oxide reduces NADPH oxidase 5 (Nox5) activity by reversible S-nitrosylation. Free Radic Biol Med 52(9):1806–1819

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Bossis G, Melchior F (2006) SUMO: regulating the regulator. Cell Div 1:13

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Pandey D, Chen F, Patel A, Wang CY, Dimitropoulou C, Patel VS, Rudic RD, Stepp DW, Fulton DJ (2011) SUMO1 negatively regulates reactive oxygen species production from NADPH oxidases. Arterioscler Thromb Vasc Biol 31(7):1634–1642

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Pandey D, Patel A, Patel V, Chen F, Qian J, Wang Y, Barman SA, Venema RC, Stepp DW, Rudic RD, Fulton DJ (2012) Expression and functional significance of NADPH oxidase 5 (Nox5) and its splice variants in human blood vessels. Am J Physiol Heart Circ Physiol 302(10):H1919–H1928

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Wang Y, Chen F, Le B, Stepp DW, Fulton DJ (2014) Impact of Nox5 polymorphisms on basal and stimulus-dependent ROS generation. PLoS One 9(7):e100102

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Chu AY, Guilianini F, Grallert H, Dupuis J, Ballantyne CM, Barratt BJ, Nyberg F, Chasman DI, Ridker PM (2012) Genome-wide association study evaluating lipoprotein-associated phospholipase A2 mass and activity at baseline and after rosuvastatin therapy. Circ Cardiovasc Genet 5(6):676–685

    Article  CAS  PubMed  Google Scholar 

  58. Han X, Hu Z, Chen J, Huang J, Huang C, Liu F, Gu C, Yang X, Hixson JE, Lu X, Wang L, Liu DP, He J, Chen S, Gu D (2017) Associations between genetic variants of NADPH oxidase-related genes and blood pressure responses to dietary sodium intervention: the GenSalt study. Am J Hypertens 30(4):427–434

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Manea A, Manea SA, Florea IC, Luca CM, Raicu M (2012) Positive regulation of NADPH oxidase 5 by proinflammatory-related mechanisms in human aortic smooth muscle cells. Free Radic Biol Med 52(9):1497–1507

    Article  CAS  PubMed  Google Scholar 

  60. Guzik TJ, Chen W, Gongora MC, Guzik B, Lob HE, Mangalat D, Hoch N, Dikalov S, Rudzinski P, Kapelak B, Sadowski J, Harrison DG (2008) Calcium-dependent NOX5 nicotinamide adenine dinucleotide phosphate oxidase contributes to vascular oxidative stress in human coronary artery disease. J Am Coll Cardiol 52(22):1803–1809

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Lambeth JD (2007) Nox enzymes, ROS, and chronic disease: an example of antagonistic pleiotropy. Free Radic Biol Med 43(3):332–347

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Jay DB, Papaharalambus CA, Seidel-Rogol B, Dikalova AE, Lassegue B, Griendling KK (2008) Nox5 mediates PDGF-induced proliferation in human aortic smooth muscle cells. Free Radic Biol Med 45(3):329–335

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Stanic B, Pandey D, Fulton DJ, Miller FJ Jr (2012) Increased epidermal growth factor-like ligands are associated with elevated vascular nicotinamide adenine dinucleotide phosphate oxidase in a primate model of atherosclerosis. Arterioscler Thromb Vasc Biol 32(10):2452–2460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Weyemi U, Redon CE, Aziz T, Choudhuri R, Maeda D, Parekh PR, Bonner MY, Arbiser JL, Bonner WM (2015) Inactivation of NADPH oxidases NOX4 and NOX5 protects human primary fibroblasts from ionizing radiation-induced DNA damage. Radiat Res 183(3):262–270

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Yu P, Han W, Villar VA, Yang Y, Lu Q, Lee H, Li F, Quinn MT, Gildea JJ, Felder RA, Jose PA (2014) Unique role of NADPH oxidase 5 in oxidative stress in human renal proximal tubule cells. Redox Biol 2:570–579

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Manea A, Manea SA, Gan AM, Constantin A, Fenyo IM, Raicu M, Muresian H, Simionescu M (2015) Human monocytes and macrophages express NADPH oxidase 5; a potential source of reactive oxygen species in atherosclerosis. Biochem Biophys Res Commun 461(1):172–179

    Article  CAS  PubMed  Google Scholar 

  67. Marzaioli V, Hurtado-Nedelec M, Pintard C, Tlili A, Marie JC, Monteiro RC, Gougerot-Pocidalo MA, Dang PM, El-Benna J (2017) NOX5 and p22phox are 2 novel regulators of human monocytic differentiation into dendritic cells. Blood 130(15):1734–1745

    Article  CAS  PubMed  Google Scholar 

  68. Accetta R, Damiano S, Morano A, Mondola P, Paterno R, Avvedimento EV, Santillo M (2016) Reactive oxygen species derived from NOX3 and NOX5 drive differentiation of human oligodendrocytes. Front Cell Neurosci 10:146

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  69. Holl M, Koziel R, Schafer G, Pircher H, Pauck A, Hermann M, Klocker H, Jansen-Durr P, Sampson N (2016) ROS signaling by NADPH oxidase 5 modulates the proliferation and survival of prostate carcinoma cells. Mol Carcinog 55(1):27–39

    Article  PubMed  CAS  Google Scholar 

  70. Shigemura T, Shiohara M, Kato M, Furuta S, Kaneda K, Morishita K, Hasegawa H, Fujii M, Gorlach A, Koike K, Kamata T (2015) Superoxide-generating Nox5alpha Is functionally required for the human T-cell leukemia virus type 1-induced cell transformation phenotype. J Virol 89(17):9080–9089

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Mahbouli S, Der Vartanian A, Ortega S, Rouge S, Vasson MP, Rossary A (2017) Leptin induces ROS via NOX5 in healthy and neoplastic mammary epithelial cells. Oncol Rep 38(5):3254–3264

    Article  CAS  PubMed  Google Scholar 

  72. Bartimoccia S, Carnevale R, Sanguigni V, De Falco E, Frati G, Loffredo L, Plebani A, Soresina A, Pignatelli P, Violi F (2016) NOX 5 is expressed in platelets from patients with chronic granulomatous disease. Thromb Haemost 116(1):198–200

    PubMed  Google Scholar 

  73. Carnesecchi S, Rougemont AL, Doroshow JH, Nagy M, Mouche S, Gumy-Pause F, Szanto I (2015) The NADPH oxidase NOX5 protects against apoptosis in ALK-positive anaplastic large-cell lymphoma cell lines. Free Radic Biol Med 84:22–29

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Hong J, Li D, Cao W (2016) Rho kinase ROCK2 mediates acid-induced NADPH oxidase NOX5-S expression in human esophageal adenocarcinoma cells. PLoS One 11(2):e0149735

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  75. Antony S, Jiang G, Wu Y, Meitzler JL, Makhlouf HR, Haines DC, Butcher D, Hoon DS, Ji J, Zhang Y, Juhasz A, Lu J, Liu H, Dahan I, Konate M, Roy KK, Doroshow JH (2017) NADPH oxidase 5 (NOX5)-induced reactive oxygen signaling modulates normoxic HIF-1alpha and p27(Kip1) expression in malignant melanoma and other human tumors. Mol Carcinog 56(12):2643–2662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Dho SH, Kim JY, Lee KP, Kwon ES, Lim JC, Kim CJ, Jeong D, Kwon KS (2017) STAT5A-mediated NOX5-L expression promotes the proliferation and metastasis of breast cancer cells. Exp Cell Res 351(1):51–58

    Article  CAS  PubMed  Google Scholar 

  77. Fu X, Beer DG, Behar J, Wands J, Lambeth D, Cao W (2006) cAMP-response element-binding protein mediates acid-induced NADPH oxidase NOX5-S expression in Barrett esophageal adenocarcinoma cells. J Biol Chem 281(29):20368–20382

    Article  CAS  PubMed  Google Scholar 

  78. Pai WY, Lo WY, Hsu T, Peng CT, Wang HJ (2017) Angiotensin-(1-7) inhibits thrombin-induced endothelial phenotypic changes and reactive oxygen species production via NADPH oxidase 5 downregulation. Front Physiol 8:994

    Article  PubMed  PubMed Central  Google Scholar 

  79. Zhu C, Yu ZB, Chen XH, Ji CB, Qian LM, Han SP (2011) DNA hypermethylation of the NOX5 gene in fetal ventricular septal defect. Exp Ther Med 2(5):1011–1015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Hahn NE, Meischl C, Kawahara T, Musters RJ, Verhoef VM, van der Velden J, Vonk AB, Paulus WJ, van Rossum AC, Niessen HW, Krijnen PA (2012) NOX5 expression is increased in intramyocardial blood vessels and cardiomyocytes after acute myocardial infarction in humans. Am J Pathol 180(6):2222–2229

    Article  CAS  PubMed  Google Scholar 

  81. Montezano A, Harvey A, Rios F, Beatie W, McPherson L, Thomson J, Holterman CE, Kennedy C, Touyz RM (2017) 151 Nox5 induces vascular dysfunction and arterial remodelling independently of blood pressure elevation in ang ii-infused nox5-expressing mice. Heart 103(Suppl 5):A111–A111

    Google Scholar 

  82. Zhang Q, Malik P, Pandey D, Gupta S, Jagnandan D, Belin de Chantemele E, Banfi B, Marrero MB, Rudic RD, Stepp DW, Fulton DJ (2008) Paradoxical activation of endothelial nitric oxide synthase by NADPH oxidase. Arterioscler Thromb Vasc Biol 28(9):1627–1633

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Pi X, Xie L, Portbury AL, Kumar S, Lockyer P, Li X, Patterson C (2014) NADPH oxidase-generated reactive oxygen species are required for stromal cell-derived factor-1alpha-stimulated angiogenesis. Arterioscler Thromb Vasc Biol 34(9):2023–2032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Gole HK, Tharp DL, Bowles DK (2014) Upregulation of intermediate-conductance Ca2+−activated K+ channels (KCNN4) in porcine coronary smooth muscle requires NADPH oxidase 5 (NOX5). PLoS One 9(8):e105337

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  85. Jha JC, Banal C, Okabe J, Gray SP, Hettige T, Chow BSM, Thallas-Bonke V, De Vos L, Holterman CE, Coughlan MT, Power DA, Skene A, Ekinci EI, Cooper ME, Touyz RM, Kennedy CR, Jandeleit-Dahm K (2017) NADPH oxidase Nox5 accelerates renal injury in diabetic nephropathy. Diabetes 66(10):2691–2703

    Article  CAS  PubMed  Google Scholar 

  86. Kaur N, Naga OS, Norell H, Al-Khami AA, Scheffel MJ, Chakraborty NG, Voelkel-Johnson C, Mukherji B, Mehrotra S (2011) T cells expanded in presence of IL-15 exhibit increased antioxidant capacity and innate effector molecules. Cytokine 55(2):307–317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Sabeur K, Ball BA (2007) Characterization of NADPH oxidase 5 in equine testis and spermatozoa. Reproduction 134(2):263–270

    Article  CAS  PubMed  Google Scholar 

  88. Juhasz A, Ge Y, Markel S, Chiu A, Matsumoto L, van Balgooy J, Roy K, Doroshow JH (2009) Expression of NADPH oxidase homologues and accessory genes in human cancer cell lines, tumours and adjacent normal tissues. Free Radic Res 43(6):523–532

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Ritsick DR, Edens WA, McCoy JW, Lambeth JD (2004) The use of model systems to study biological functions of Nox/Duox enzymes. Biochem Soc Symp (71):85–96

    Article  CAS  Google Scholar 

  90. Suh YA, Arnold RS, Lassegue B, Shi J, Xu X, Sorescu D, Chung AB, Griendling KK, Lambeth JD (1999) Cell transformation by the superoxide-generating oxidase Mox1. Nature 401(6748):79–82

    Article  CAS  PubMed  Google Scholar 

  91. Antony S, Wu Y, Hewitt SM, Anver MR, Butcher D, Jiang G, Meitzler JL, Liu H, Juhasz A, Lu J, Roy KK, Doroshow JH (2013) Characterization of NADPH oxidase 5 expression in human tumors and tumor cell lines with a novel mouse monoclonal antibody. Free Radic Biol Med 65:497–508

    Article  CAS  PubMed  Google Scholar 

  92. Hong J, Li D, Wands J, Souza R, Cao W (2013) Role of NADPH oxidase NOX5-S, NF-kappaB, and DNMT1 in acid-induced p16 hypermethylation in Barrett’s cells. Am J Physiol Cell Physiol 305(10):C1069–C1079

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Mochizuki T, Furuta S, Mitsushita J, Shang WH, Ito M, Yokoo Y, Yamaura M, Ishizone S, Nakayama J, Konagai A, Hirose K, Kiyosawa K, Kamata T (2006) Inhibition of NADPH oxidase 4 activates apoptosis via the AKT/apoptosis signal-regulating kinase 1 pathway in pancreatic cancer PANC-1 cells. Oncogene 25(26):3699–3707

    Article  CAS  PubMed  Google Scholar 

  94. Kamiguti AS, Serrander L, Lin K, Harris RJ, Cawley JC, Allsup DJ, Slupsky JR, Krause KH, Zuzel M (2005) Expression and activity of NOX5 in the circulating malignant B cells of hairy cell leukemia. J Immunol 175(12):8424–8430

    Article  CAS  PubMed  Google Scholar 

  95. Zhou X, Li D, Resnick MB, Wands J, Cao W (2013) NADPH oxidase NOX5-S and nuclear factor kappaB1 mediate acid-induced microsomal prostaglandin E synthase-1 expression in Barrett’s esophageal adenocarcinoma cells. Mol Pharmacol 83(5):978–990

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Li D, Cao W (2014) Role of intracellular calcium and NADPH oxidase NOX5-S in acid-induced DNA damage in Barrett’s cells and Barrett’s esophageal adenocarcinoma cells. Am J Physiol Gastrointest Liver Physiol 306(10):G863–G872

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Si J, Behar J, Wands J, Beer DG, Lambeth D, Chin YE, Cao W (2008) STAT5 mediates PAF-induced NADPH oxidase NOX5-S expression in Barrett’s esophageal adenocarcinoma cells. Am J Physiol Gastrointest Liver Physiol 294(1):G174–G183

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by NIH grants R01HL124773, R01HL125926.

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Authors and Affiliations

  1. Vascular Biology Center, Medical College of Georgia at Augusta University, Augusta, GA, USA

    David J. R. Fulton

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  1. David J. R. Fulton
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Correspondence to David J. R. Fulton .

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Editors and Affiliations

  1. Conway Institute, School of Medicine, University College Dublin, Dublin, Ireland

    Ulla G. Knaus

  2. Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    Thomas L. Leto

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Fulton, D.J.R. (2019). The Molecular Regulation and Functional Roles of NOX5. In: Knaus, U., Leto, T. (eds) NADPH Oxidases. Methods in Molecular Biology, vol 1982. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9424-3_22

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  • DOI: https://doi.org/10.1007/978-1-4939-9424-3_22

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9423-6

  • Online ISBN: 978-1-4939-9424-3

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