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Cytotoxin-induced NADPH oxides activation: roles in regulation of cell death

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Abstract

Numerous studies have shown that a variety of cytotoxic agents can activate the NADPH oxidase system and induce redox-dependent regulation of cellular functions. Cytotoxin-induced NADPH oxidase activation may either exert cytoprotective actions (e.g., survival, proliferation, and stress tolerance) or cause cell death. Here we summarize the experimental evidence showing the context-dependent dichotomous effects of NADPH oxidase on cell fate under cytotoxic stress conditions and the potential redox signaling mechanisms underlying this phenomenon. Clearly, it is difficult to create a unified paradigm on the toxicological implications of NADPH oxidase activation in response to cytotoxic stimuli. We suggest that interventional strategies targeting the NADPH oxidase system to prevent the adverse impacts of cytotoxins need to be contemplated in a stimuli- and cell type-specific manner.

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References

  • Abramov AY, Canevari L, Duchen MR (2004) Beta-amyloid peptides induce mitochondrial dysfunction and oxidative stress in astrocytes and death of neurons through activation of NADPH oxidase. J Neurosci 24(2):565–575. doi:10.1523/JNEUROSCI.4042-03.2004

    CAS  PubMed  Google Scholar 

  • Aguado A, Galan M, Zhenyukh O et al (2013) Mercury induces proliferation and reduces cell size in vascular smooth muscle cells through MAPK, oxidative stress and cyclooxygenase-2 pathways. Toxicol Appl Pharmacol 268(2):188–200

    CAS  PubMed  Google Scholar 

  • Aki T, Funakoshi T, Unuma K, Uemura K (2013) Impairment of autophagy: from hereditary disorder to drug intoxication. Toxicology 311(3):205–215

    CAS  PubMed  Google Scholar 

  • Amara N, Bachoual R, Desmard M et al (2007) Diesel exhaust particles induce matrix metalloprotease-1 in human lung epithelial cells via a NADP(H) oxidase/NOX4 redox-dependent mechanism. Am J Physiol Lung Cell Mol Physiol 293(1):L170–L181

    CAS  PubMed  Google Scholar 

  • Anilkumar N, Weber R, Zhang M, Brewer A, Shah AM (2008) Nox4 and nox2 NADPH oxidases mediate distinct cellular redox signaling responses to agonist stimulation. Arterioscler Thromb Vasc Biol 28(7):1347–1354

    CAS  PubMed  Google Scholar 

  • Asano H, Horinouchi T, Mai Y et al (2012) Nicotine- and tar-free cigarette smoke induces cell damage through reactive oxygen species newly generated by PKC-dependent activation of NADPH oxidase. J Pharmacol Sci 118(2):275–287

    CAS  PubMed  Google Scholar 

  • Babior BM (1999) NADPH oxidase: an update. Blood 93(5):1464–1476

    CAS  PubMed  Google Scholar 

  • Banfi B, Molnar G, Maturana A et al (2001) A Ca(2+)-activated NADPH oxidase in testis, spleen, and lymph nodes. J Biol Chem 276(40):37594–37601

    CAS  PubMed  Google Scholar 

  • Banfi B, Malgrange B, Knisz J, Steger K, Dubois-Dauphin M, Krause KH (2004a) NOX3, a superoxide-generating NADPH oxidase of the inner ear. J Biol Chem 279(44):46065–46072. doi:10.1074/jbc.M403046200

    CAS  PubMed  Google Scholar 

  • Banfi B, Tirone F, Durussel I et al (2004b) Mechanism of Ca2+ activation of the NADPH oxidase 5 (NOX5). J Biol Chem 279(18):18583–18591

    CAS  PubMed  Google Scholar 

  • Barchowsky A, Klei LR, Dudek EJ, Swartz HM, James PE (1999) Stimulation of reactive oxygen, but not reactive nitrogen species, in vascular endothelial cells exposed to low levels of arsenite. Free Radic Biol Med 27(11–12):1405–1412

    CAS  PubMed  Google Scholar 

  • Basuroy S, Bhattacharya S, Leffler CW, Parfenova H (2009) Nox4 NADPH oxidase mediates oxidative stress and apoptosis caused by TNF-{alpha} in cerebral vascular endothelial cells. Am J Physiol Cell Physiol 296(3):C422–C432

    CAS  PubMed Central  PubMed  Google Scholar 

  • Becker S, Soukup JM, Gallagher JE (2002) Differential particulate air pollution induced oxidant stress in human granulocytes, monocytes and alveolar macrophages. Toxicol In Vitro 16(3):209–218

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • BelAiba RS, Djordjevic T, Petry A et al (2007) NOX5 variants are functionally active in endothelial cells. Free Radic Biol Med 42(4):446–459

    CAS  PubMed  Google Scholar 

  • Bolt AM, Klimecki WT (2012) Autophagy in toxicology: self-consumption in times of stress and plenty. J Appl Toxicol 32(7):465–479. doi:10.1002/jat.1787

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cassatella MA, Bazzoni F, Flynn RM, Dusi S, Trinchieri G, Rossi F (1990) Molecular basis of interferon-gamma and lipopolysaccharide enhancement of phagocyte respiratory burst capability. Studies on the gene expression of several NADPH oxidase components. J Biol Chem 265(33):20241–20246

    CAS  PubMed  Google Scholar 

  • Chakraborty PK, Lee WK, Molitor M, Wolff NA, Thevenod F (2010) Cadmium induces Wnt signaling to upregulate proliferation and survival genes in sub-confluent kidney proximal tubule cells. Mol Cancer 9:102

    PubMed Central  PubMed  Google Scholar 

  • Chan EC, Jiang F, Peshavariya HM, Dusting GJ (2009) Regulation of cell proliferation by NADPH oxidase-mediated signaling: potential roles in tissue repair, regenerative medicine and tissue engineering. Pharmacol Ther 122(2):97–108

    CAS  PubMed  Google Scholar 

  • Check J, Byrd CL, Menio J, Rippe RA, Hines IN, Wheeler MD (2010) Src kinase participates in LPS-induced activation of NADPH oxidase. Mol Immunol 47(4):756–762

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chen YC, Lin-Shiau SY, Lin JK (1998) Involvement of reactive oxygen species and caspase 3 activation in arsenite-induced apoptosis. J Cell Physiol 177(2):324–333

    CAS  PubMed  Google Scholar 

  • 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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chen L, Xu B, Liu L et al (2011) Cadmium induction of reactive oxygen species activates the mTOR pathway, leading to neuronal cell death. Free Radic Biol Med 50(5):624–632

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chen F, Haigh S, Barman S, Fulton DJ (2012) From form to function: the role of Nox4 in the cardiovascular system. Front Physiol 3:412. doi:10.3389/fphys.2012.00412

    CAS  PubMed Central  PubMed  Google Scholar 

  • 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

    CAS  PubMed  Google Scholar 

  • Cheng SE, Lee IT, Lin CC, Kou YR, Yang CM (2010) Cigarette smoke particle-phase extract induces HO-1 expression in human tracheal smooth muscle cells: role of the c-Src/NADPH oxidase/MAPK/Nrf2 signaling pathway. Free Radic Biol Med 48(10):1410–1422

    CAS  PubMed  Google Scholar 

  • Chiarelli R, Roccheri MC (2012) Heavy metals and metalloids as autophagy inducing agents: focus on cadmium and arsenic. Cells 1(3):597–616

    CAS  PubMed Central  PubMed  Google Scholar 

  • Choi YJ, Shin HS, Choi HS et al (2014) Uric acid induces fat accumulation via generation of endoplasmic reticulum stress and SREBP-1c activation in hepatocytes. Lab Invest 94(10):1114–1125

    CAS  PubMed  Google Scholar 

  • Chou WC, Jie C, Kenedy AA, Jones RJ, Trush MA, Dang CV (2004) Role of NADPH oxidase in arsenic-induced reactive oxygen species formation and cytotoxicity in myeloid leukemia cells. Proc Natl Acad Sci USA 101(13):4578–4583. doi:10.1073/pnas.0306687101

    CAS  PubMed Central  PubMed  Google Scholar 

  • Coant N, Mkaddem SB, Pedruzzi E et al (2010) NADPH oxidase 1 modulates WNT and NOTCH1 signaling to control the fate of proliferative progenitor cells in the colon. Mol Cell Biol 30(11):2636–2650

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cooper KL, Liu KJ, Hudson LG (2009) Enhanced ROS production and redox signaling with combined arsenite and UVA exposure: contribution of NADPH oxidase. Free Radic Biol Med 47(4):381–388

    CAS  PubMed Central  PubMed  Google Scholar 

  • Csordas A, Kreutmayer S, Ploner C et al (2011) Cigarette smoke extract induces prolonged endoplasmic reticulum stress and autophagic cell death in human umbilical vein endothelial cells. Cardiovasc Res 92(1):141–148

    CAS  PubMed  Google Scholar 

  • Dandapat A, Hu C, Sun L, Mehta JL (2007) Small concentrations of oxLDL induce capillary tube formation from endothelial cells via LOX-1-dependent redox-sensitive pathway. Arterioscler Thromb Vasc Biol 27(11):2435–2442

    CAS  PubMed  Google Scholar 

  • De Deken X, Wang D, Many MC et al (2000) Cloning of two human thyroid cDNAs encoding new members of the NADPH oxidase family. J Biol Chem 275(30):23227–23233

    PubMed  Google Scholar 

  • de Pablo-Latorre R, Saide A, Polishhuck EV, Nusco E, Fraldi A, Ballabio A (2012) Impaired parkin-mediated mitochondrial targeting to autophagosomes differentially contributes to tissue pathology in lysosomal storage diseases. Hum Mol Genet 21(8):1770–1781

    PubMed Central  PubMed  Google Scholar 

  • Dong F, Zhang X, Li SY et al (2005) Possible involvement of NADPH oxidase and JNK in homocysteine-induced oxidative stress and apoptosis in human umbilical vein endothelial cells. Cardiovasc Toxicol 5(1):9–20

    CAS  PubMed  Google Scholar 

  • Dong Z, Wang L, Xu J et al (2009) Promotion of autophagy and inhibition of apoptosis by low concentrations of cadmium in vascular endothelial cells. Toxicol In Vitro 23(1):105–110

    CAS  PubMed  Google Scholar 

  • Dupuy C, Ohayon R, Valent A, Noel-Hudson MS, Deme D, Virion A (1999) Purification of a novel flavoprotein involved in the thyroid NADPH oxidase. Cloning of the porcine and human cdnas. J Biol Chem 274(52):37265–37269

    CAS  PubMed  Google Scholar 

  • Eid AA, Ford BM, Block K et al (2010) AMP-activated protein kinase (AMPK) negatively regulates Nox4-dependent activation of p53 and epithelial cell apoptosis in diabetes. J Biol Chem 285(48):37503–37512

    CAS  PubMed Central  PubMed  Google Scholar 

  • Farrow MA, Chumbler NM, Lapierre LA et al (2013) Clostridium difficile toxin B-induced necrosis is mediated by the host epithelial cell NADPH oxidase complex. Proc Natl Acad Sci USA 110(46):18674–18679

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fu P, Mohan V, Mansoor S, Tiruppathi C, Sadikot RT, Natarajan V (2013) Role of nicotinamide adenine dinucleotide phosphate-reduced oxidase proteins in Pseudomonas aeruginosa-induced lung inflammation and permeability. Am J Respir Cell Mol Biol 48(4):477–488

    CAS  PubMed Central  PubMed  Google Scholar 

  • Fukumoto S, Hsieh CM, Maemura K et al (2001) Akt participation in the Wnt signaling pathway through Dishevelled. J Biol Chem 276(20):17479–17483. doi:10.1074/jbc.C000880200

    CAS  PubMed  Google Scholar 

  • Geiszt M, Kopp JB, Varnai P, Leto TL (2000) Identification of renox, an NAD(P)H oxidase in kidney. Proc Natl Acad Sci USA 97(14):8010–8014

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ghatak S, Biswas A, Dhali GK, Chowdhury A, Boyer JL, Santra A (2011) Oxidative stress and hepatic stellate cell activation are key events in arsenic induced liver fibrosis in mice. Toxicol Appl Pharmacol 251(1):59–69

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gorissen SH, Hristova M, Habibovic A et al (2013) Dual oxidase-1 is required for airway epithelial cell migration and bronchiolar reepithelialization after injury. Am J Respir Cell Mol Biol 48(3):337–345

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gough DR, Cotter TG (2011) Hydrogen peroxide: a Jekyll and Hyde signalling molecule. Cell Death Dis 2:e213

    CAS  PubMed Central  PubMed  Google Scholar 

  • Griendling KK, Sorescu D, Ushio-Fukai M (2000) NAD(P)H oxidase: role in cardiovascular biology and disease. Circ Res 86(5):494–501

    CAS  PubMed  Google Scholar 

  • Haj FG, Markova B, Klaman LD, Bohmer FD, Neel BG (2003) Regulation of receptor tyrosine kinase signaling by protein tyrosine phosphatase-1B. J Biol Chem 278(2):739–744

    CAS  PubMed  Google Scholar 

  • Han JE, Choi JW (2012) Control of JNK for an activation of NADPH oxidase in LPS-stimulated BV2 microglia. Arch Pharm Res 35(4):709–715. doi:10.1007/s12272-012-0415-1

    CAS  PubMed  Google Scholar 

  • Hasegawa T, Kikuyama M, Sakurai K et al (2002) Mechanism of superoxide anion production by hepatic sinusoidal endothelial cells and Kupffer cells during short-term ethanol perfusion in the rat. Liver 22(4):321–329

    CAS  PubMed  Google Scholar 

  • He C, Zhu H, Zhang W et al (2013) 7-Ketocholesterol induces autophagy in vascular smooth muscle cells through Nox4 and Atg4B. Am J Pathol 183(2):626–637

    CAS  PubMed Central  PubMed  Google Scholar 

  • Heinloth A, Heermeier K, Raff U, Wanner C, Galle J (2000) Stimulation of NADPH oxidase by oxidized low-density lipoprotein induces proliferation of human vascular endothelial cells. J Am Soc Nephrol 11(10):1819–1825

    CAS  PubMed  Google Scholar 

  • Hoyer-Hansen M, Jaattela M (2007) Connecting endoplasmic reticulum stress to autophagy by unfolded protein response and calcium. Cell Death Differ 14(9):1576–1582

    CAS  PubMed  Google Scholar 

  • Huang J, Canadien V, Lam GY et al (2009) Activation of antibacterial autophagy by NADPH oxidases. Proc Natl Acad Sci USA 106(15):6226–6231

    CAS  PubMed Central  PubMed  Google Scholar 

  • Irani K (2000) Oxidant signaling in vascular cell growth, death, and survival: a review of the roles of reactive oxygen species in smooth muscle and endothelial cell mitogenic and apoptotic signaling. Circ Res 87(3):179–183

    CAS  PubMed  Google Scholar 

  • Itoh T, Terazawa R, Kojima K et al (2011) Cisplatin induces production of reactive oxygen species via NADPH oxidase activation in human prostate cancer cells. Free Radic Res 45(9):1033–1039. doi:10.3109/10715762.2011.591391

    CAS  PubMed  Google Scholar 

  • Jaimes EA, DeMaster EG, Tian RX, Raij L (2004) Stable compounds of cigarette smoke induce endothelial superoxide anion production via NADPH oxidase activation. Arterioscler Thromb Vasc Biol 24(6):1031–1036

    CAS  PubMed  Google Scholar 

  • Jang HJ, Hwang S, Cho KY, Kim DK, Chay KO, Kim JK (2008) Taxol induces oxidative neuronal cell death by enhancing the activity of NADPH oxidase in mouse cortical cultures. Neurosci Lett 443(1):17–22

    CAS  PubMed  Google Scholar 

  • Jiang F, Drummond GR, Dusting GJ (2004) Suppression of oxidative stress in the endothelium and vascular wall. Endothelium 11(2):79–88

    CAS  PubMed  Google Scholar 

  • Jiang F, Guo N, Dusting GJ (2008) Modulation of nicotinamide adenine dinucleotide phosphate oxidase expression and function by 3′,4′-dihydroxyflavonol in phagocytic and vascular cells. J Pharmacol Exp Ther 324(1):261–269

    CAS  PubMed  Google Scholar 

  • 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(1):218–242. doi:10.1124/pr.110.002980

    CAS  PubMed  Google Scholar 

  • Jiao J, Dou L, Li M et al (2012) NADPH oxidase 2 plays a critical role in dysfunction and apoptosis of pancreatic beta-cells induced by very low-density lipoprotein. Mol Cell Biochem 370(1–2):103–113. doi:10.1007/s11010-012-1402-z

    CAS  PubMed  Google Scholar 

  • Kajla S, Mondol AS, Nagasawa A et al (2012) A crucial role for Nox 1 in redox-dependent regulation of Wnt–beta-catenin signaling. FASEB J 26(5):2049–2059

    CAS  PubMed  Google Scholar 

  • Kandadi MR, Hua Y, Ma H et al (2010) Anthrax lethal toxin suppresses murine cardiomyocyte contractile function and intracellular Ca2+ handling via a NADPH oxidase-dependent mechanism. PLoS One 5(10):e13335. doi:10.1371/journal.pone.0013335

    PubMed Central  PubMed  Google Scholar 

  • Kanzawa T, Zhang L, Xiao L, Germano IM, Kondo Y, Kondo S (2005) Arsenic trioxide induces autophagic cell death in malignant glioma cells by upregulation of mitochondrial cell death protein BNIP3. Oncogene 24(6):980–991

    CAS  PubMed  Google Scholar 

  • Kaspar JW, Niture SK, Jaiswal AK (2009) Nrf 2:INrf2 (Keap1) signaling in oxidative stress. Free Radic Biol Med 47(9):1304–1309

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kikuchi H, Hikage M, Miyashita H, Fukumoto M (2000) NADPH oxidase subunit, gp91(phox) homologue, preferentially expressed in human colon epithelial cells. Gene 254(1–2):237–243

    CAS  PubMed  Google Scholar 

  • Kim H, Jung Y, Shin BS et al (2010a) Redox regulation of lipopolysaccharide-mediated sulfiredoxin induction, which depends on both AP-1 and Nrf2. J Biol Chem 285(45):34419–34428

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kim HJ, Lee JH, Kim SJ et al (2010b) Roles of NADPH oxidases in cisplatin-induced reactive oxygen species generation and ototoxicity. J Neurosci 30(11):3933–3946

    CAS  PubMed  Google Scholar 

  • Komiya Y, Habas R (2008) Wnt signal transduction pathways. Organogenesis 4(2):68–75

    PubMed Central  PubMed  Google Scholar 

  • Kwon J, Lee SR, Yang KS et al (2004) Reversible oxidation and inactivation of the tumor suppressor PTEN in cells stimulated with peptide growth factors. Proc Natl Acad Sci USA 101(47):16419–16424

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lambeth JD (2004) NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol 4(3):181–189

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lassegue B, Clempus RE (2003) Vascular NAD(P)H oxidases: specific features, expression, and regulation. Am J Physiol Regul Integr Comp Physiol 285(2):R277–R297

    CAS  PubMed  Google Scholar 

  • Lavigne MC, Eppihimer MJ (2005) Cigarette smoke condensate induces MMP-12 gene expression in airway-like epithelia. Biochem Biophys Res Commun 330(1):194–203

    CAS  PubMed  Google Scholar 

  • Lee SR, Kwon KS, Kim SR, Rhee SG (1998) Reversible inactivation of protein-tyrosine phosphatase 1B in A431 cells stimulated with epidermal growth factor. J Biol Chem 273(25):15366–15372

    CAS  PubMed  Google Scholar 

  • Lee JK, Edderkaoui M, Truong P et al (2007) NADPH oxidase promotes pancreatic cancer cell survival via inhibiting JAK2 dephosphorylation by tyrosine phosphatases. Gastroenterology 133(5):1637–1648

    CAS  PubMed  Google Scholar 

  • Lee SH, Park DW, Park SC et al (2009) Calcium-independent phospholipase A2beta-Akt signaling is involved in lipopolysaccharide-induced NADPH oxidase 1 expression and foam cell formation. J Immunol 183(11):7497–7504

    CAS  PubMed  Google Scholar 

  • Lee IT, Shih RH, Lin CC, Chen JT, Yang CM (2012) Role of TLR4/NADPH oxidase/ROS-activated p38 MAPK in VCAM-1 expression induced by lipopolysaccharide in human renal mesangial cells. Cell Commun Signal 10(1):33

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lemarie A, Bourdonnay E, Morzadec C, Fardel O, Vernhet L (2008) Inorganic arsenic activates reduced NADPH oxidase in human primary macrophages through a Rho kinase/p38 kinase pathway. J Immunol 180(9):6010–6017

    CAS  PubMed  Google Scholar 

  • Li L, Frei B (2009) Prolonged exposure to LPS increases iron, heme, and p22phox levels and NADPH oxidase activity in human aortic endothelial cells: inhibition by desferrioxamine. Arterioscler Thromb Vasc Biol 29(5):732–738

    CAS  PubMed Central  PubMed  Google Scholar 

  • Li JM, Shah AM (2002) Intracellular localization and preassembly of the NADPH oxidase complex in cultured endothelial cells. J Biol Chem 277(22):19952–19960

    CAS  PubMed  Google Scholar 

  • Li JM, Shah AM (2003) Mechanism of endothelial cell NADPH oxidase activation by angiotensin II. Role of the p47phox subunit. J Biol Chem 278(14):12094–12100

    CAS  PubMed  Google Scholar 

  • Li WG, Stoll LL, Rice JB et al (2003) Activation of NAD(P)H oxidase by lipid hydroperoxides: mechanism of oxidant-mediated smooth muscle cytotoxicity. Free Radic Biol Med 34(7):937–946

    CAS  PubMed  Google Scholar 

  • Li G, Scull C, Ozcan L, Tabas I (2010) NADPH oxidase links endoplasmic reticulum stress, oxidative stress, and PKR activation to induce apoptosis. J Cell Biol 191(6):1113–1125

    CAS  PubMed Central  PubMed  Google Scholar 

  • Li YN, Xi MM, Guo Y, Hai CX, Yang WL, Qin XJ (2014) NADPH oxidase-mitochondria axis-derived ROS mediate arsenite-induced HIF-1alpha stabilization by inhibiting prolyl hydroxylases activity. Toxicol Lett 224(2):165–174

    CAS  PubMed  Google Scholar 

  • Lino-dos-Santos-Franco A, Correa-Costa M, Durao AC et al (2011) Formaldehyde induces lung inflammation by an oxidant and antioxidant enzymes mediated mechanism in the lung tissue. Toxicol Lett 207(3):278–285

    CAS  PubMed  Google Scholar 

  • Liu F, Chernoff J (1997) Protein tyrosine phosphatase 1B interacts with and is tyrosine phosphorylated by the epidermal growth factor receptor. Biochem J 327(Pt 1):139–145

    CAS  PubMed Central  PubMed  Google Scholar 

  • Loughlin DT, Artlett CM (2010) Precursor of advanced glycation end products mediates ER-stress-induced caspase-3 activation of human dermal fibroblasts through NAD(P)H oxidase 4. PLoS One 5(6):e11093. doi:10.1371/journal.pone.0011093

    PubMed Central  PubMed  Google Scholar 

  • Lu TH, Tseng TJ, Su CC et al (2013) Arsenic induces reactive oxygen species-caused neuronal cell apoptosis through JNK/ERK-mediated mitochondria-dependent and GRP 78/CHOP-regulated pathways. Toxicol Lett 224(1):130–140

    PubMed  Google Scholar 

  • Lynn S, Gurr JR, Lai HT, Jan KY (2000) NADH oxidase activation is involved in arsenite-induced oxidative DNA damage in human vascular smooth muscle cells. Circ Res 86(5):514–519

    CAS  PubMed  Google Scholar 

  • Ma J, Wang Y, Zheng D, Wei M, Xu H, Peng T (2013) Rac1 signalling mediates doxorubicin-induced cardiotoxicity through both reactive oxygen species-dependent and -independent pathways. Cardiovasc Res 97(1):77–87

    CAS  PubMed  Google Scholar 

  • Mahadev K, Motoshima H, Wu X et al (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(5):1844–1854

    CAS  PubMed Central  PubMed  Google Scholar 

  • Martinez Flores K, Uribe Marin BC, Souza Arroyo V et al (2013) Hepatocytes display a compensatory survival response against cadmium toxicity by a mechanism mediated by EGFR and Src. Toxicol In Vitro 27(3):1031–1042

    CAS  PubMed  Google Scholar 

  • Martyn KD, Frederick LM, von Loehneysen K, Dinauer MC, Knaus UG (2006) Functional analysis of Nox4 reveals unique characteristics compared to other NADPH oxidases. Cell Signal 18(1):69–82

    CAS  PubMed  Google Scholar 

  • Mary VS, Theumer MG, Arias SL, Rubinstein HR (2012) Reactive oxygen species sources and biomolecular oxidative damage induced by aflatoxin B1 and fumonisin B1 in rat spleen mononuclear cells. Toxicology 302(2–3):299–307

    CAS  PubMed  Google Scholar 

  • Matsunaga T, Hokari S, Koyama I, Harada T, Komoda T (2003) NF-kappa B activation in endothelial cells treated with oxidized high-density lipoprotein. Biochem Biophys Res Commun 303(1):313–319

    CAS  PubMed  Google Scholar 

  • Miyano K, Ueno N, Takeya R, Sumimoto H (2006) Direct involvement of the small GTPase Rac in activation of the superoxide-producing NADPH oxidase Nox1. J Biol Chem 281(31):21857–21868

    CAS  PubMed  Google Scholar 

  • Narendra D, Tanaka A, Suen DF, Youle RJ (2008) Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol 183(5):795–803

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ni Z, Hou S, Barton CH, Vaziri ND (2004) Lead exposure raises superoxide and hydrogen peroxide in human endothelial and vascular smooth muscle cells. Kidney Int 66(6):2329–2336

    CAS  PubMed  Google Scholar 

  • Ni HM, Bockus A, Boggess N, Jaeschke H, Ding WX (2012) Activation of autophagy protects against acetaminophen-induced hepatotoxicity. Hepatology 55(1):222–232. doi:10.1002/hep.24690

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nisimoto Y, Diebold BA, Constentino-Gomes D, Lambeth JD (2014) Nox4: a hydrogen peroxide-generating oxygen sensor. Biochemistry 53(31):5111–5120. doi:10.1021/bi500331y

    CAS  PubMed  Google Scholar 

  • Orosz Z, Csiszar A, Labinskyy N et al (2007) Cigarette smoke-induced proinflammatory alterations in the endothelial phenotype: role of NAD(P)H oxidase activation. Am J Physiol Heart Circ Physiol 292(1):H130–H139

    CAS  PubMed  Google Scholar 

  • Orrenius S, Kaminskyy VO, Zhivotovsky B (2013) Autophagy in toxicology: Cause or consequence? Annu Rev Pharmacol Toxicol 53:275–297. doi:10.1146/annurev-pharmtox-011112-140210

    CAS  PubMed  Google Scholar 

  • Paffenholz R, Bergstrom RA, Pasutto F et al (2004) Vestibular defects in head-tilt mice result from mutations in Nox3, encoding an NADPH oxidase. Genes Dev 18(5):486–491. doi:10.1101/gad.1172504

    CAS  PubMed Central  PubMed  Google Scholar 

  • Park HS, Jung HY, Park EY, Kim J, Lee WJ, Bae YS (2004) Cutting edge: direct interaction of TLR4 with NAD(P)H oxidase 4 isozyme is essential for lipopolysaccharide-induced production of reactive oxygen species and activation of NF-kappa B. J Immunol 173(6):3589–3593

    CAS  PubMed  Google Scholar 

  • Park L, Anrather J, Zhou P et al (2005) NADPH-oxidase-derived reactive oxygen species mediate the cerebrovascular dysfunction induced by the amyloid beta peptide. J Neurosci 25(7):1769–1777

    CAS  PubMed  Google Scholar 

  • Pedruzzi E, Guichard C, Ollivier V et al (2004) NAD(P)H oxidase Nox-4 mediates 7-ketocholesterol-induced endoplasmic reticulum stress and apoptosis in human aortic smooth muscle cells. Mol Cell Biol 24(24):10703–10717

    CAS  PubMed Central  PubMed  Google Scholar 

  • Peshavariya H, Dusting GJ, Jiang F et al (2009a) NADPH oxidase isoform selective regulation of endothelial cell proliferation and survival. Naunyn Schmiedebergs Arch Pharmacol 380(2):193–204. doi:10.1007/s00210-009-0413-0

    CAS  PubMed  Google Scholar 

  • Peshavariya H, Jiang F, Taylor CJ, Chang CWT, Dusting GJ (2009b) Translation-linked mRNA destabilization during serum-induced Nox4 expression in human endothelial cells. Antioxid Redox Signal 11(10):2399–2408

    CAS  PubMed  Google Scholar 

  • Pettigrew CA, Clerkin JS, Cotter TG (2012) DUOX enzyme activity promotes AKT signalling in prostate cancer cells. Anticancer Res 32(12):5175–5181

    CAS  PubMed  Google Scholar 

  • Pourrut B, Perchet G, Silvestre J, Cecchi M, Guiresse M, Pinelli E (2008) Potential role of NADPH-oxidase in early steps of lead-induced oxidative burst in Vicia faba roots. J Plant Physiol 165(6):571–579

    CAS  PubMed  Google Scholar 

  • Puca R, Nardinocchi L, Starace G et al (2010) Nox1 is involved in p53 deacetylation and suppression of its transcriptional activity and apoptosis. Free Radic Biol Med 48(10):1338–1346

    CAS  PubMed  Google Scholar 

  • Qian Y, Liu KJ, Chen Y, Flynn DC, Castranova V, Shi X (2005) Cdc42 regulates arsenic-induced NADPH oxidase activation and cell migration through actin filament reorganization. J Biol Chem 280(5):3875–3884

    CAS  PubMed  Google Scholar 

  • Qin L, Crews FT (2012) NADPH oxidase and reactive oxygen species contribute to alcohol-induced microglial activation and neurodegeneration. J Neuroinflammation 9:5

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rockwell P, Martinez J, Papa L, Gomes E (2004) Redox regulates COX-2 upregulation and cell death in the neuronal response to cadmium. Cell Signal 16(3):343–353

    CAS  PubMed  Google Scholar 

  • Rueckschloss U, Galle J, Holtz J, Zerkowski HR, Morawietz H (2001) Induction of NAD(P)H oxidase by oxidized low-density lipoprotein in human endothelial cells: antioxidative potential of hydroxymethylglutaryl coenzyme A reductase inhibitor therapy. Circulation 104(15):1767–1772

    CAS  PubMed  Google Scholar 

  • Rump TJ, Muneer PMA, Szlachetka AM et al (2010) Acetyl-L-carnitine protects neuronal function from alcohol-induced oxidative damage in the brain. Free Radic Biol Med 49(10):1494–1504

    CAS  PubMed Central  PubMed  Google Scholar 

  • Salmeen A, Park BO, Meyer T (2010) The NADPH oxidases NOX4 and DUOX2 regulate cell cycle entry via a p53-dependent pathway. Oncogene 29(31):4473–4484

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sancho P, Mainez J, Crosas-Molist E et al (2012) NADPH oxidase NOX4 mediates stellate cell activation and hepatocyte cell death during liver fibrosis development. PLoS One 7(9):e45285. doi:10.1371/journal.pone.0045285

    CAS  PubMed Central  PubMed  Google Scholar 

  • Santos CX, Tanaka LY, Wosniak J, Laurindo FR (2009) Mechanisms and implications of reactive oxygen species generation during the unfolded protein response: roles of endoplasmic reticulum oxidoreductases, mitochondrial electron transport, and NADPH oxidase. Antioxid Redox Signal 11(10):2409–2427. doi:10.1089/ARS.2009.2625

    CAS  PubMed  Google Scholar 

  • Scherz-Shouval R, Shvets E, Fass E, Shorer H, Gil L, Elazar Z (2007) Reactive oxygen species are essential for autophagy and specifically regulate the activity of Atg4. EMBO J 26(7):1749–1760

    CAS  PubMed Central  PubMed  Google Scholar 

  • Schonthal AH (2012) Endoplasmic reticulum stress: its role in disease and novel prospects for therapy. Scientifica (Cairo) 2012:857516. doi:10.6064/2012/857516

    Google Scholar 

  • Sciarretta S, Zhai P, Shao D et al (2013) Activation of NADPH oxidase 4 in the endoplasmic reticulum promotes cardiomyocyte autophagy and survival during energy stress through the protein kinase RNA-activated-like endoplasmic reticulum kinase/eukaryotic initiation factor 2alpha/activating transcription factor 4 pathway. Circ Res 113(11):1253–1264

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shelat PB, Chalimoniuk M, Wang JH et al (2008) Amyloid beta peptide and NMDA induce ROS from NADPH oxidase and AA release from cytosolic phospholipase A2 in cortical neurons. J Neurochem 106(1):45–55

    CAS  PubMed  Google Scholar 

  • Shen S, Kepp O, Michaud M et al (2011) Association and dissociation of autophagy, apoptosis and necrosis by systematic chemical study. Oncogene 30(45):4544–4556

    CAS  PubMed  Google Scholar 

  • Shi K, Egawa K, Maegawa H et al (2004) Protein-tyrosine phosphatase 1B associates with insulin receptor and negatively regulates insulin signaling without receptor internalization. J Biochem 136(1):89–96

    CAS  PubMed  Google Scholar 

  • Shih RH, Cheng SE, Hsiao LD, Kou YR, Yang CM (2011) Cigarette smoke extract upregulates heme oxygenase-1 via PKC/NADPH oxidase/ROS/PDGFR/PI3K/Akt pathway in mouse brain endothelial cells. J Neuroinflammation 8:104

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shimizu S, Kanaseki T, Mizushima N et al (2004) Role of Bcl-2 family proteins in a non-apoptotic programmed cell death dependent on autophagy genes. Nat Cell Biol 6(12):1221–1228

    CAS  PubMed  Google Scholar 

  • Simon F, Fernandez R (2009) Early lipopolysaccharide-induced reactive oxygen species production evokes necrotic cell death in human umbilical vein endothelial cells. J Hypertens 27(6):1202–1216. doi:10.1097/HJH.0b013e328329e31c

    CAS  PubMed  Google Scholar 

  • Sipkens JA, Krijnen PA, Meischl C et al (2007) Homocysteine affects cardiomyocyte viability: concentration-dependent effects on reversible flip-flop, apoptosis and necrosis. Apoptosis 12(8):1407–1418. doi:10.1007/s10495-007-0077-5

    CAS  PubMed Central  PubMed  Google Scholar 

  • Smith KR, Klei LR, Barchowsky A (2001) Arsenite stimulates plasma membrane NADPH oxidase in vascular endothelial cells. Am J Physiol Lung Cell Mol Physiol 280(3):L442–L449

    CAS  PubMed  Google Scholar 

  • Sobhakumari A, Schickling BM, Love-Homan L et al (2013) NOX4 mediates cytoprotective autophagy induced by the EGFR inhibitor erlotinib in head and neck cancer cells. Toxicol Appl Pharmacol 272(3):736–745

    CAS  PubMed  Google Scholar 

  • Souza V, del Escobar MC, Bucio L, Hernandez E, Gomez-Quiroz LE, Gutierrez Ruiz MC (2009) NADPH oxidase and ERK1/2 are involved in cadmium induced-STAT3 activation in HepG2 cells. Toxicol Lett 187(3):180–186

    CAS  PubMed  Google Scholar 

  • Straub AC, Clark KA, Ross MA et al (2008) Arsenic-stimulated liver sinusoidal capillarization in mice requires NADPH oxidase-generated superoxide. J Clin Invest 118(12):3980–3989

    CAS  PubMed Central  PubMed  Google Scholar 

  • Suh YA, Arnold RS, Lassegue B et al (1999) Cell transformation by the superoxide-generating oxidase Mox1. Nature 401(6748):79–82

    CAS  PubMed  Google Scholar 

  • Suzuki S, Arnold LL, Pennington KL, Kakiuchi-Kiyota S, Cohen SM (2009) Effects of co-administration of dietary sodium arsenite and an NADPH oxidase inhibitor on the rat bladder epithelium. Toxicology 261(1–2):41–46

    CAS  PubMed  Google Scholar 

  • Szymczyk KH, Kerr BA, Freeman TA, Adams CS, Steinbeck MJ (2006) Involvement of hydrogen peroxide in the differentiation and apoptosis of preosteoclastic cells exposed to arsenite. Biochem Pharmacol 72(6):761–769

    CAS  PubMed  Google Scholar 

  • Terada LS (2006) Specificity in reactive oxidant signaling: think globally, act locally. J Cell Biol 174(5):615–623

    CAS  PubMed Central  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  • Tsai KH, Wang WJ, Lin CW et al (2012) NADPH oxidase-derived superoxide anion-induced apoptosis is mediated via the JNK-dependent activation of NF-kappaB in cardiomyocytes exposed to high glucose. J Cell Physiol 227(4):1347–1357. doi:10.1002/jcp.22847

    CAS  PubMed  Google Scholar 

  • Tseng HY, Liu ZM, Huang HS (2012) NADPH oxidase-produced superoxide mediates EGFR transactivation by c-Src in arsenic trioxide-stimulated human keratinocytes. Arch Toxicol 86(6):935–945. doi:10.1007/s00204-012-0856-9

    CAS  PubMed  Google Scholar 

  • Tumur Z, Niwa T (2009) Indoxyl sulfate inhibits nitric oxide production and cell viability by inducing oxidative stress in vascular endothelial cells. Am J Nephrol 29(6):551–557

    CAS  PubMed  Google Scholar 

  • Ueno N, Takeya R, Miyano K, Kikuchi H, Sumimoto H (2005) The NADPH oxidase Nox3 constitutively produces superoxide in a p22phox-dependent manner: its regulation by oxidase organizers and activators. J Biol Chem 280(24):23328–23339

    CAS  PubMed  Google Scholar 

  • Ushio-Fukai M (2009) Compartmentalization of redox signaling through NADPH oxidase-derived ROS. Antioxid Redox Signal 11(6):1289–1299. doi:10.1089/ARS.2008.2333

    CAS  PubMed Central  PubMed  Google Scholar 

  • Veit F, Pak O, Egemnazarov B et al (2013) Function of NADPH oxidase 1 in pulmonary arterial smooth muscle cells after monocrotaline-induced pulmonary vascular remodeling. Antioxid Redox Signal 19(18):2213–2231. doi:10.1089/ars.2012.4904

    CAS  PubMed  Google Scholar 

  • Vousden KH (2006) Outcomes of p53 activation–spoilt for choice. J Cell Sci 119(Pt 24):5015–5020

    CAS  PubMed  Google Scholar 

  • Wagner B, Ricono JM, Gorin Y et al (2007) Mitogenic signaling via platelet-derived growth factor beta in metanephric mesenchymal cells. J Am Soc Nephrol 18(11):2903–2911

    CAS  PubMed  Google Scholar 

  • Wang X, Son YO, Chang Q et al (2011) NADPH oxidase activation is required in reactive oxygen species generation and cell transformation induced by hexavalent chromium. Toxicol Sci 123(2):399–410

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang L, Son YO, Ding S et al (2012) Ethanol enhances tumor angiogenesis in vitro induced by low-dose arsenic in colon cancer cells through hypoxia-inducible factor 1 alpha pathway. Toxicol Sci 130(2):269–280

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wang Q, Zhu J, Zhang K et al (2013) Induction of cytoprotective autophagy in PC-12 cells by cadmium. Biochem Biophys Res Commun 438(1):186–192

    CAS  PubMed  Google Scholar 

  • Watanabe H, Miyamoto Y, Honda D et al (2013a) p-Cresyl sulfate causes renal tubular cell damage by inducing oxidative stress by activation of NADPH oxidase. Kidney Int 83(4):582–592

    CAS  PubMed  Google Scholar 

  • Watanabe I, Tatebe J, Namba S, Koizumi M, Yamazaki J, Morita T (2013b) Activation of aryl hydrocarbon receptor mediates indoxyl sulfate-induced monocyte chemoattractant protein-1 expression in human umbilical vein endothelial cells. Circ J 77(1):224–230

    CAS  PubMed  Google Scholar 

  • Wen JW, Hwang JT, Kelly GM (2012) Reactive oxygen species and Wnt signalling crosstalk patterns mouse extraembryonic endoderm. Cell Signal 24(12):2337–2348

    CAS  PubMed  Google Scholar 

  • Xie Y, Xiao F, Luo L, Zhong C (2014) Activation of autophagy protects against ROS-mediated mitochondria-dependent apoptosis in L-02 hepatocytes induced by Cr(VI). Cell Physiol Biochem 33(3):705–716

    CAS  PubMed  Google Scholar 

  • Xu Y, Fang F, Miriyala S et al (2013) KEAP1 is a redox sensitive target that arbitrates the opposing radiosensitive effects of parthenolide in normal and cancer cells. Cancer Res 73(14):4406–4417

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yan F, Wang Y, Wu X et al (2014) Nox4 and redox signaling mediate TGF-beta-induced endothelial cell apoptosis and phenotypic switch. Cell Death Dis 5:e1010

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yeh CM, Chien PS, Huang HJ (2007) Distinct signalling pathways for induction of MAP kinase activities by cadmium and copper in rice roots. J Exp Bot 58(3):659–671

    CAS  PubMed  Google Scholar 

  • Yen YP, Tsai KS, Chen YW, Huang CF, Yang RS, Liu SH (2012) Arsenic induces apoptosis in myoblasts through a reactive oxygen species-induced endoplasmic reticulum stress and mitochondrial dysfunction pathway. Arch Toxicol 86(6):923–933. doi:10.1007/s00204-012-0864-9

    CAS  PubMed  Google Scholar 

  • Yi F, Zhang AY, Li N et al (2006) Inhibition of ceramide-redox signaling pathway blocks glomerular injury in hyperhomocysteinemic rats. Kidney Int 70(1):88–96

    CAS  PubMed  Google Scholar 

  • Yin QQ, Dong CF, Dong SQ et al (2012) AGEs induce cell death via oxidative and endoplasmic reticulum stresses in both human SH-SY5Y neuroblastoma cells and rat cortical neurons. Cell Mol Neurobiol 32(8):1299–1309. doi:10.1007/s10571-012-9856-9

    CAS  PubMed  Google Scholar 

  • Yu L, Alva A, Su H et al (2004) Regulation of an ATG7-beclin 1 program of autophagic cell death by caspase-8. Science 304(5676):1500–1502. doi:10.1126/science.1096645

    CAS  PubMed  Google Scholar 

  • Yun MR, Park HM, Seo KW, Lee SJ, Im DS, Kim CD (2010) 5-Lipoxygenase plays an essential role in 4-HNE-enhanced ROS production in murine macrophages via activation of NADPH oxidase. Free Radic Res 44(7):742–750. doi:10.3109/10715761003758122

    CAS  PubMed  Google Scholar 

  • Zeng KW, Song FJ, Wang YH et al (2014) Induction of hepatoma carcinoma cell apoptosis through activation of the JNK-nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-ROS self-driven death signal circuit. Cancer Lett 353(2):220–231

    CAS  PubMed  Google Scholar 

  • Zhang Z, Wang X, Cheng S et al (2011) Reactive oxygen species mediate arsenic induced cell transformation and tumorigenesis through Wnt/beta-catenin pathway in human colorectal adenocarcinoma DLD1 cells. Toxicol Appl Pharmacol 256(2):114–121

    CAS  PubMed  Google Scholar 

  • Zhao Y, McLaughlin D, Robinson E et al (2010) Nox2 NADPH oxidase promotes pathologic cardiac remodeling associated with Doxorubicin chemotherapy. Cancer Res 70(22):9287–9297

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhou LL, Hou FF, Wang GB et al (2009) Accumulation of advanced oxidation protein products induces podocyte apoptosis and deletion through NADPH-dependent mechanisms. Kidney Int 76(11):1148–1160

    PubMed  Google Scholar 

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Acknowledgments

This work was supported by grants from the National 973 Basic Research Program of China (2013CB530700) and National Natural Science Foundation of China (31471087).

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    1. Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, 107 Wen Hua Xi Road, Jinan, 250012, Shandong Province, China

      Yongtao Zhang, Xiaolei Bi & Fan Jiang

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    1. Yongtao Zhang
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    Correspondence to Fan Jiang.

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    Yongtao Zhang and Xiaolei Bi have contributed equally to this work.

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    Zhang, Y., Bi, X. & Jiang, F. Cytotoxin-induced NADPH oxides activation: roles in regulation of cell death. Arch Toxicol 89, 991–1006 (2015). https://doi.org/10.1007/s00204-015-1476-y

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