• 1
    Pryor, W. A., Houk, K. N., Foote, C. S., Fukuto, J. M., Ignarro, L. J., et al. (2006) Free radical biology and medicine: it's a gas, man! Am. J. Physiol. Regul. Integr. Comp. Physiol. 291, R491511.
  • 2
    Davies, M. J. (2003) Singlet oxygen-mediated damage to proteins and its consequences. Biochem. Biophys. Res. Commun. 305, 761770.
  • 3
    Cadenas, E and Davies, KJ (2000) Mitochondrial free radical generation, oxidative stress, and aging. Free Radic. Biol. Med. 29, 222230.
  • 4
    Lenaz, G. (2001) The mitochondrial production of reactive oxygen species: mechanisms and implications in human pathology. IUBMB Life 52, 159164.
  • 5
    Muller, F. L., Liu, Y., and Van Remmen, H. (2004) Complex III releases superoxide to both sides of the inner mitochondrial membrane. J. Biol. Chem. 279, 4906449073.
  • 6
    Moghaddas, S., Hoppel, C. L., and Lesnefsky, E. J. (2003) Aging defect at the QO site of complex III augments oxyradical production in rat heart interfibrillar mitochondria. Arch. Biochem. Biophys. 414, 5966.
  • 7
    Kowaltowski, A. J., de Souza-Pinto, N. C., Castilho, R. F., and Vercesi, A. E. (2009) Mitochondria and reactive oxygen species. Free Radic. Biol. Med. 47, 333343.
  • 8
    Hayes, P. and Knaus, U. G. (2013) Balancing reactive oxygen species in the epigenome: NADPH oxidases as target and perpetrator. Antioxid. Redox Signal. 18, 19371945.
  • 9
    Kleikers, P. W., Wingler, K., Hermans, J. J., Diebold, I., Altenhofer, S., et al. (2012) NADPH oxidases as a source of oxidative stress and molecular target in ischemia/reperfusion injury. J. Mol. Med. (Berl) 90, 13911406.
  • 10
    Maron, B. A. and Michel, T. (2012) Subcellular localization of oxidants and redox modulation of endothelial nitric oxide synthase. Circ. J. 76, 24972512.
  • 11
    Burgoyne, J. R., Mongue-Din, H., Eaton, P., and Shah, A. M. (2012) Redox signaling in cardiac physiology and pathology. Circ. Res. 111, 10911106.
  • 12
    Murphy, M. P. (2012) Modulating mitochondrial intracellular location as a redox signal. Sci. Signal. 5, pe39.
  • 13
    Eliades, A., Matsuura, S., and Ravid, K. (2012) Oxidases and reactive oxygen species during hematopoiesis: a focus on megakaryocytes. J. Cell. Physiol. 227, 33553362.
  • 14
    Kakihana, T., Nagata, K., and Sitia, R. (2012) Peroxides and peroxidases in the endoplasmic reticulum: integrating redox homeostasis and oxidative folding. Antioxid. Redox Signal. 16, 763771.
  • 15
    Dodson, M., Darley-Usmar, V., and Zhang, J. (2013) Cellular metabolic and autophagic pathways: traffic control by redox signaling. Free Radic. Biol. Med. 63, 207221.
  • 16
    Fridovich, I. (2013) Oxygen: how do we stand it? Med. Princ. Pract. 22, 131137.
  • 17
    Halliwell, B. (2012) Free radicals and antioxidants: updating a personal view. Nutr. Rev. 70, 257265.
  • 18
    Sohal, R. S. and Orr, W. C. (2012) The redox stress hypothesis of aging. Free Radic. Biol. Med. 52, 539555.
  • 19
    Limon-Pacheco, J. and Gonsebatt, M. E. (2009) The role of antioxidants and antioxidant-related enzymes in protective responses to environmentally induced oxidative stress. Mutat. Res. 674, 137147.
  • 20
    Buettner, G. R. (2011) Superoxide dismutase in redox biology: the roles of superoxide and hydrogen peroxide. Anticancer Agents Med. Chem. 11, 341346.
  • 21
    Darley-Usmar, V. and Halliwell, B. (1996) Blood radicals: reactive nitrogen species, reactive oxygen species, transition metal ions, and the vascular system. Pharm. Res. 13, 649662.
  • 22
    Jeong, W., Bae, S. H., Toledano, M. B., and Rhee, S. G. (2012) Role of sulfiredoxin as a regulator of peroxiredoxin function and regulation of its expression. Free Radic. Biol. Med. 53, 447456.
  • 23
    Rhee, S. G., Woo, H. A., Kil, I. S., and Bae, S. H. (2012) Peroxiredoxin functions as a peroxidase and a regulator and sensor of local peroxides. J. Biol. Chem. 287, 44034410.
  • 24
    Paulsen, C. E. and Carroll, K. S. (2010) Orchestrating redox signaling networks through regulatory cysteine switches. ACS Chem. Biol. 5, 4762.
  • 25
    Kalyanaraman, B. (2013) Teaching the basics of redox biology to medical and graduate students: oxidants, antioxidants and disease mechanisms. Redox Biol. 1, 244257.
  • 26
    Roede, J. R., Uppal, K., Liang, Y., Promislow, D. E., Wachtman, L. M., et al. (2013) Characterization of plasma thiol redox potential in a common marmoset model of aging. Redox Biol. 1, 387393.
  • 27
    Carr, A. C., Zhu, B. Z., and Frei, B. (2000) Potential antiatherogenic mechanisms of ascorbate (vitamin C) and alpha-tocopherol (vitamin E). Circ. Res. 87, 349354.
  • 28
    Low, F. M., Hampton, M. B., and Winterbourn, C. C. (2008) Peroxiredoxin 2 and peroxide metabolism in the erythrocyte. Antioxid. Redox Signal. 10, 16211630.
  • 29
    Ansley, D. M. and Wang, B. (2013) Oxidative stress and myocardial injury in the diabetic heart. J. Pathol. 229, 232241.
  • 30
    van Golen, R. F., van Gulik, T. M., and Heger, M. (2012) Mechanistic overview of reactive species-induced degradation of the endothelial glycocalyx during hepatic ischemia/reperfusion injury. Free Radic. Biol. Med. 52, 13821402.
  • 31
    Drummond, G. R., Selemidis, S., Griendling, K. K., and Sobey, C. G. (2011) Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets. Nat. Rev. Drug Discov. 10, 453471.
  • 32
    Rains, J. L. and Jain, S. K. (2011) Oxidative stress, insulin signaling, and diabetes. Free Radic. Biol. Med. 50, 567575.
  • 33
    Giacco, F. and Brownlee M (2010) Oxidative stress and diabetic complications. Circ. Res. 107, 10581070.
  • 34
    Stadler, K. (2011) Peroxynitrite-driven mechanisms in diabetes and insulin resistance—the latest advances. Curr. Med. Chem. 18, 280290.
  • 35
    Ghanizadeh, A., Akhondzadeh, S., Hormozi, M., Makarem, A., Abotorabi-Zarchi, M., et al. (2012) Glutathione-related factors and oxidative stress in autism, a review. Curr. Med. Chem. 19, 40004005.
  • 36
    Weinberg, F. and Chandel, N. S. (2009) Reactive oxygen species-dependent signaling regulates cancer. Cell Mol. Life Sci. 66, 36633673.
  • 37
    Chen, Y., Jungsuwadee, P., Vore, M., Butterfield, D. A., and St. Clair, D. K. (2007) Collateral damage in cancer chemotherapy: oxidative stress in nontargeted tissues. Mol. Interv. 7, 147156.
  • 38
    Erickson, J. R., He, B. J., Grumbach, I. M., and Anderson, M. E. (2011) CaMKII in the cardiovascular system: sensing redox states. Physiol. Rev. 91, 889915.
  • 39
    Bonini, M. G., Gabel, S. A., Ranguelova, K., Stadler, K., Derose, E. F., et al. (2009) Direct magnetic resonance evidence for peroxymonocarbonate involvement in the cu,zn-superoxide dismutase peroxidase catalytic cycle. J. Biol. Chem. 284, 1461814627.
  • 40
    Pehar, M., Vargas, M. R., Robinson, K. M., Cassina, P., England, P., et al. (2006) Peroxynitrite transforms nerve growth factor into an apoptotic factor for motor neurons. Free Radic. Biol. Med. 41, 16321644.
  • 41
    Ehrenshaft, M., Silva, S. O., Perdivara, I., Bilski, P., Sik, R. H., et al. (2009) Immunological detection of N-formylkynurenine in oxidized proteins. Free Radic. Biol. Med. 46, 12601266.
  • 42
    Ehrenshaft, M., Zhao, B., Andley, U. P., Mason, R. P., Roberts, J. E. (2011) Immunological detection of N-formylkynurenine in porphyrin-mediated photooxided lens alpha-crystallin. Photochem. Photobiol. 87, 13211329.
  • 43
    Bonini, M. G., Radi, R., Ferrer-Sueta, G., Ferreira, A. M., and Augusto, O. (1999) Direct EPR detection of the carbonate radical anion produced from peroxynitrite and carbon dioxide. J. Biol. Chem. 274, 1080210806.
  • 44
    Meli, R., Nauser, T., Latal, P., and Koppenol, W. H. (2002) Reaction of peroxynitrite with carbon dioxide: intermediates and determination of the yield of CO3*- and NO2*. J. Biol. Inorg. Chem. 7, 3136.
  • 45
    Bonini, M. G., Fernandes, D. C., and Augusto, O. (2004) Albumin oxidation to diverse radicals by the peroxidase activity of Cu,Zn-superoxide dismutase in the presence of bicarbonate or nitrite: diffusible radicals produce cysteinyl and solvent-exposed and -unexposed tyrosyl radicals. Biochemistry 43, 344351.
  • 46
    Augusto, O., Bonini, M. G., Amanso, A. M., Linares, E., Santos, C. C., et al. (2002) Nitrogen dioxide and carbonate radical anion: two emerging radicals in biology. Free Radic. Biol. Med. 32, 841859.
  • 47
    Buettner, G. R. (1993) The pecking order of free radicals and antioxidants: lipid peroxidation, alpha-tocopherol, and ascorbate. Arch. Biochem. Biophys. 300, 535543.
  • 48
    Xiao, C., Palmer, D. A., Wesolowski, D. J., Lovitz, S. B., King, D. W. (2002) Carbon dioxide effects on luminol and 1,10-phenanthroline chemiluminescence. Anal. Chem. 74, 22102216.
  • 49
    Beckman, J. S., Beckman, T. W., Chen, J., Marshall, P. A., Freeman, B. A. (1990) Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc. Natl. Acad. Sci. USA 87, 16201624.
  • 50
    Shchepin, R., Moller, M. N., Kim, H. Y., Hatch, D. M., Bartesaghi, S., et al. (2010) Tyrosine-lipid peroxide adducts from radical termination: para coupling and intramolecular Diels-Alder cyclization. J. Am. Chem. Soc. 132, 1749017500.
  • 51
    Rubbo, H., Parthasarathy, S., Barnes, S., Kirk, M., Kalyanaraman, B., et al. (1995) Nitric oxide inhibition of lipoxygenase-dependent liposome and low-density lipoprotein oxidation: termination of radical chain propagation reactions and formation of nitrogen-containing oxidized lipid derivatives. Arch. Biochem. Biophys. 324, 1525.
  • 52
    Sikora, A., Zielonka, J., Lopez, M., Dybala-Defratyka, A., Joseph, J., et al. (2011) Reaction between peroxynitrite and boronates: EPR spin-trapping, HPLC analyses, and quantum mechanical study of the free radical pathway. Chem. Res. Toxicol. 24, 687697.
  • 53
    Murphy, M. P., Holmgren, A., Larsson, N. G., Halliwell, B., Chang, C. J., et al. (2011) Unraveling the biological roles of reactive oxygen species. Cell. Metab. 13, 361366.
  • 54
    Waypa, G. B. and Schumacker, P. T. (2008) Oxygen sensing in hypoxic pulmonary vasoconstriction: using new tools to answer an age-old question. Exp. Physiol. 93, 133138.
  • 55
    Santos, J. H., Meyer, J. N., Mandavilli, B. S., and Van Houten, B. (2006) Quantitative PCR-based measurement of nuclear and mitochondrial DNA damage and repair in mammalian cells. Methods Mol. Biol. 314, 183199.
  • 56
    Nelson, K. J., Klomsiri, C., Codreanu, S. G., Soito, L., Liebler, D. C., et al. (2010) Use of dimedone-based chemical probes for sulfenic acid detection methods to visualize and identify labeled proteins. Methods Enzymol. 473, 95115.
  • 57
    Pan, J. and Carroll, K. S. (2013) Chemical biology approaches to study protein cysteine sulfenylation. Biopolymers. doi: 10.1002/bip.22255.
  • 58
    Janssen-Heininger, Y. M., Mossman, B. T., Heintz, N. H., Forman, H. J., Kalyanaraman, B., et al. (2008) Redox-based regulation of signal transduction: principles, pitfalls, and promises. Free Radic. Biol. Med. 45, 117.
  • 59
    Zielonka, J., Lambeth, J. D., and Kalyanaraman, B. (2013) On the use of L-012, a luminol-based chemiluminescent probe, for detecting superoxide and identifying inhibitors of NADPH oxidase: a reevaluation. Free Radic. Biol. Med. 65C, 13101314.
  • 60
    Zielonka, J., Joseph, J., Sikora, A., and Kalyanaraman, B. (2013) Real-time monitoring of reactive oxygen and nitrogen species in a multiwell plate using the diagnostic marker products of specific probes. Methods Enzymol. 526, 145157.
  • 61
    Kalyanaraman, B., Dranka, B. P., Hardy, M., Michalski, R., and Zielonka, J. (2014) HPLC-based monitoring of products formed from hydroethidine-based fluorogenic probes—the ultimate approach for intra- and extracellular superoxide detection. Biochim. Biophys. Acta 1840, 739744.
  • 62
    Zielonka, J., Zielonka, M., Sikora, A., Adamus, J., Joseph, J., et al. (2012) Global profiling of reactive oxygen and nitrogen species in biological systems: high-throughput real-time analyses. J. Biol. Chem. 287, 29842995.
  • 63
    Zielonka, J., Vasquez-Vivar, J., and Kalyanaraman, B. (2008) Detection of 2-hydroxyethidium in cellular systems: a unique marker product of superoxide and hydroethidine. Nat. Protoc. 3, 821.
  • 64
    Rhee, S. G., Chang, T. S., Jeong, W., and Kang, D. (2010) Methods for detection and measurement of hydrogen peroxide inside and outside of cells. Mol. Cells 29, 539549.
  • 65
    Sies, H. (1993) Strategies of antioxidant defense. Eur. J. Biochem. 215, 213219.
  • 66
    Ogilby, P. R. and Foote, C. S. (1983) Chemistry of singlet oxygen. 42. Effect of solvent, solvent isotopic-substitution, and temperature on the lifetime of singlet molecular-oxygen (1-Delta-G). J. Am. Chem. Soc. 105, 34233430.
  • 67
    Egorov, S. Y., Kamalov, V. F., Koroteev, N. I., Krasnovsky, A. A., Toleutaev, B. N., et al. (1989) Rise and decay kinetics of photosensitized singlet oxygen luminescence in water—measurements with nanosecond time-correlated single photon-counting technique. Chem. Phys. Lett. 163, 421424.
  • 68
    Kuimova, M. K., Balaz, M., Anderson, H. L., and Ogilby, P. R. (2009) Intramolecular rotation in a porphyrin dimer controls singlet oxygen production. J. Am. Chem. Soc. 131, 7948+.
  • 69
    Koppenol, W. H. (1976) Reactions involving singlet oxygen and superoxide anion. Nature 262, 420421.
  • 70
    Greer, A. (2006) Christopher Foote's discovery of the role of singlet oxygen (O-1(2) ((1)Delta(g))) in photosensitized oxidation reactions. Acc. Chem. Res. 39, 797804.
  • 71
    Hodges, G. R., Young, M. J., Paul, T., and Ingold, K. U. (2000) How should xanthine oxidase-generated superoxide yields be measured? Free Radic. Biol. Med. 29, 434441.
  • 72
    Bonini, M. G., Miyamoto, S., Di Mascio, P., and Augusto, O. (2004) Production of the carbonate radical anion during xanthine oxidase turnover in the presence of bicarbonate. J. Biol. Chem. 279, 5183651843.
  • 73
    Vasquez-Vivar, J., Kalyanaraman, B., Martasek, P., Hogg, N., Masters, B. S., et al. (1998) Superoxide generation by endothelial nitric oxide synthase: the influence of cofactors. Proc. Natl. Acad. Sci. USA 95, 92209225.
  • 74
    Cai, H., Griendling, K. K., and Harrison, D. G. (2003) The vascular NAD(P)H oxidases as therapeutic targets in cardiovascular diseases. Trends Pharmacol. Sci. 24, 471478.
  • 75
    Giorgio, M., Trinei, M., Migliaccio, E., and Pelicci, P. G. (2007) Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals? Nat. Rev. Mol. Cell. Biol. 8, 722728.
  • 76
    Bredt, D. S. and Snyder, S. H. (1990) Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme. Proc. Natl. Acad. Sci. USA 87, 682685.
  • 77
    Palacios, M., Knowles, R. G., Palmer, R. M., and Moncada, S. (1989) Nitric oxide from L-arginine stimulates the soluble guanylate cyclase in adrenal glands. Biochem. Biophys. Res. Commun. 165, 802809.
  • 78
    Knowles, R. G., Palacios, M., Palmer, R. M., and Moncada, S. (1989) Formation of nitric oxide from L-arginine in the central nervous system: a transduction mechanism for stimulation of the soluble guanylate cyclase. Proc. Natl. Acad. Sci. USA 86, 51595162.
  • 79
    Thomas, D. D., Liu, X., Kantrow, S. P., and Lancaster, J. R., Jr. (2001) The biological lifetime of nitric oxide: implications for the perivascular dynamics of NO and O2. Proc. Natl. Acad. Sci. USA 98, 355360.
  • 80
    Koppenol, W. H., Bounds, P. L., Nauser, T., Kissner, R., and Ruegger, H. (2012) Peroxynitrous acid: controversy and consensus surrounding an enigmatic oxidant. Dalton Trans. 41, 1377913787.
  • 81
    Ferrer-Sueta, G. and Radi, R. (2009) Chemical biology of peroxynitrite: kinetics, diffusion, and radicals. ACS Chem. Biol. 4, 161177.
  • 82
    Bonini, M. G. and Augusto, O. (2001) Carbon dioxide stimulates the production of thiyl, sulfinyl, and disulfide radical anion from thiol oxidation by peroxynitrite. J. Biol. Chem. 276, 97499754.
  • 83
    Augusto, O., Bonini, M. G., and Trindade, D. (2004) Spin trapping of glutathiyl and protein radicals produced from nitric oxide-derived oxidants. Free Radic. Biol. Med. 36, 12241232.
  • 84
    Klomsiri, C., Karplus, P. A., and Poole, L. B. (2011) Cysteine-based redox switches in enzymes. Antioxid. Redox Signal. 14, 10651077.
  • 85
    Dalle-Donne, I., Milzani, A., Gagliano, N., Colombo, R., Giustarini, D., et al. (2008) Molecular mechanisms and potential clinical significance of S-glutathionylation. Antioxid. Redox Signal. 10, 445473.
  • 86
    Kettenhofen, N. J. and Wood, M. J. (2010) Formation, reactivity, and detection of protein sulfenic acids. Chem. Res. Toxicol. 23, 16331646.
  • 87
    Hobbs, G. A., Bonini, M. G., Gunawardena, H. P., Chen, X., Campbell, S. L. (2013) Glutathiolated Ras: characterization and implications for Ras activation. Free Radic. Biol. Med. 57, 221229.
  • 88
    Davis, M. F., Zhou, L., Ehrenshaft, M., Ranguelova, K., Gunawardena, H. P., et al. (2012) Detection of Ras GTPase protein radicals through immuno-spin trapping. Free Radic. Biol. Med. 53, 13391345.
  • 89
    Salmeen, A., Andersen, J. N., Myers, M. P., Meng, T. C., Hinks, J. A., et al. (2003) Redox regulation of protein tyrosine phosphatase 1B involves a sulphenyl-amide intermediate. Nature 423, 769773.
  • 90
    Lim, J. C., Choi, H. I., Park, Y. S., Nam, H. W., Woo, H. A., et al. (2008) Irreversible oxidation of the active-site cysteine of peroxiredoxin to cysteine sulfonic acid for enhanced molecular chaperone activity. J. Biol. Chem. 283, 2887328880.
  • 91
    Roussel, X., Kriznik, A., Richard, C., Rahuel-Clermont, S., and Branlant, G. (2009) Catalytic mechanism of Sulfiredoxin from Saccharomyces cerevisiae passes through an oxidized disulfide sulfiredoxin intermediate that is reduced by thioredoxin. J. Biol. Chem. 284, 3304833055.
  • 92
    Jeong, W., Park, S. J., Chang, T. S., Lee, D. Y., and Rhee, S. G. (2006) Molecular mechanism of the reduction of cysteine sulfinic acid of peroxiredoxin to cysteine by mammalian sulfiredoxin. J. Biol. Chem. 281, 1440014407.
  • 93
    Bajic, A., Spasic, M., Andjus, P. R., Savic, D., Parabucki, A., et al. (2013) Fluctuating vs. continuous exposure to H2O2: the effects on mitochondrial membrane potential, intracellular calcium, and NF-kappaB in astroglia. PLoS One 8, e76383.
  • 94
    Diers, A. R., Broniowska, K. A., and Hogg, N. (2013) Nitrosative stress and redox-cycling agents synergize to cause mitochondrial dysfunction and cell death in endothelial cells. Redox Biol. 1, 17.
  • 95
    Li, N., Brun, T., Cnop, M., Cunha, D. A., Eizirik, D. L., et al. (2009) Transient oxidative stress damages mitochondrial machinery inducing persistent beta-cell dysfunction. J. Biol. Chem. 284, 2360223612.
  • 96
    Forman, H. J., Maiorino, M., and Ursini, F. (2010) Signaling functions of reactive oxygen species. Biochemistry 49, 835842.
  • 97
    Finkel, T. (2012) From sulfenylation to sulfhydration: what a thiolate needs to tolerate. Sci. Signal. 5, pe10.
  • 98
    Barbouti, A., Amorgianiotis, C., Kolettas, E., Kanavaros, P., and Galaris, D. (2007) Hydrogen peroxide inhibits caspase-dependent apoptosis by inactivating procaspase-9 in an iron-dependent manner. Free Radic. Biol. Med. 43, 13771387.
  • 99
    Connor, K. M., Subbaram, S., Regan, K. J., Nelson, K. K., Mazurkiewicz, J. E., et al. (2005) Mitochondrial H2O2 regulates the angiogenic phenotype via PTEN oxidation. J. Biol. Chem. 280, 1691616924.
  • 100
    Bogeski, I., Bozem, M., Sternfeld, L., Hofer, H. W., and Schulz, I. (2006) Inhibition of protein tyrosine phosphatase 1B by reactive oxygen species leads to maintenance of Ca2+ influx following store depletion in HEK 293 cells. Cell Calcium 40, 110.
  • 101
    Whisler, R. L., Goyette, M. A., Grants, I. S., and Newhouse, Y. G. (1995) Sublethal levels of oxidant stress stimulate multiple serine/threonine kinases and suppress protein phosphatases in Jurkat T cells. Arch. Biochem. Biophys. 319, 2335.
  • 102
    Aggeli, I. K., Beis, I., and Gaitanaki, C. (2008) Oxidative stress and calpain inhibition induce alpha B-crystallin phosphorylation via p38-MAPK and calcium signalling pathways in H9c2 cells. Cell Signal. 20, 12921302.
  • 103
    Headlam, H. A., Gracanin, M., Rodgers, K. J., and Davies, M. J. (2006) Inhibition of cathepsins and related proteases by amino acid, peptide, and protein hydroperoxides. Free Radic. Biol. Med. 40, 15391548.
  • 104
    Parker, B. W., Schwessinger, E. A., Jakob, U., and Gray, M. J. (2013) The RclR protein is a reactive chlorine-specific transcription factor in Escherichia coli. J. Biol. Chem. 288, 3257432584.
  • 105
    Tajc, S. G., Tolbert, B. S., Basavappa, R., and Miller, B. L. (2004) Direct determination of thiol pKa by isothermal titration microcalorimetry. J. Am. Chem. Soc. 126, 1050810509.
  • 106
    Denu, J. M., Zhou, G., Guo, Y., and Dixon, J. E. (1995) The catalytic role of aspartic acid-92 in a human dual-specific protein-tyrosine-phosphatase. Biochemistry 34, 33963403.
  • 107
    Angeloni, C., Motori, E., Fabbri, D., Malaguti, M., Leoncini, E., et al. (2011) H2O2 preconditioning modulates phase II enzymes through p38 MAPK and PI3K/Akt activation. Am. J. Physiol. Heart Circ. Physiol. 300, H21962205.
  • 108
    Emerling, B. M., Weinberg, F., Snyder, C., Burgess, Z., Mutlu, G. M., et al. (2009) Hypoxic activation of AMPK is dependent on mitochondrial ROS but independent of an increase in AMP/ATP ratio. Free Radic. Biol. Med. 46, 13861391.
  • 109
    Chen, K., Albano, A., Ho, A., and Keaney, J. F., Jr. (2003) Activation of p53 by oxidative stress involves platelet-derived growth factor-beta receptor-mediated ataxia telangiectasia mutated (ATM) kinase activation. J. Biol. Chem. 278, 3952739533.
  • 110
    Guo, Y., Du, J., and Kwiatkowski, D. J. (2013) Molecular dissection of AKT activation in lung cancer cell lines. Mol. Cancer Res. 11, 282293.
  • 111
    Dar, A. C., Das, T. K., Shokat, K. M., and Cagan, R. L. (2012) Chemical genetic discovery of targets and anti-targets for cancer polypharmacology. Nature 486, 8084.
  • 112
    Cho, N. L., Lin, C. I., Du, J., Whang, E. E., Ito, H., et al. (2012) Global tyrosine kinome profiling of human thyroid tumors identifies Src as a promising target for invasive cancers. Biochem. Biophys. Res. Commun. 421, 508513.
  • 113
    Duncan, J. S., Whittle, M. C., Nakamura, K., Abell, A. N., Midland, A. A., et al. (2012) Dynamic reprogramming of the kinome in response to targeted MEK inhibition in triple-negative breast cancer. Cell 149, 307321.
  • 114
    Song, M. S., Salmena, L., and Pandolfi, P. P. (2012) The functions and regulation of the PTEN tumour suppressor. Nat. Rev. Mol. Cell. Biol. 13, 283296.
  • 115
    Knobbe, C. B., Lapin, V., Suzuki, A., and Mak, T. W. (2008) The roles of PTEN in development, physiology and tumorigenesis in mouse models: a tissue-by-tissue survey. Oncogene 27, 53985415.
  • 116
    Di Cristofano, A. and Pandolfi, P. P. (2000) The multiple roles of PTEN in tumor suppression. Cell 100, 387390.
  • 117
    Mester, J. and Eng C (2013) When overgrowth bumps into cancer: the PTEN-opathies. Am. J. Med. Genet. C Semin. Med. Genet. 163, 114121.
  • 118
    Kwabi-Addo, B., Giri, D., Schmidt, K., Podsypanina, K., Parsons, R., et al. (2001) Haploinsufficiency of the Pten tumor suppressor gene promotes prostate cancer progression. Proc Natl Acad Sci USA 98, 1156311568.
  • 119
    Li, Y., Podsypanina, K., Liu, X., Crane, A., Tan, L. K., et al. (2001) Deficiency of Pten accelerates mammary oncogenesis in MMTV-Wnt-1 transgenic mice. BMC Mol Biol 2, 2.
  • 120
    Chen, M. L., Xu, P. Z., Peng, X. D., Chen, W. S., Guzman, G., et al. (2006) The deficiency of Akt1 is sufficient to suppress tumor development in Pten+/− mice. Genes Dev. 20, 15691574.
  • 121
    Bayascas, J. R., Leslie, N. R., Parsons, R., Fleming, S., and Alessi, D. R. (2005) Hypomorphic mutation of PDK1 suppresses tumorigenesis in PTEN(+/−) mice. Curr. Biol. 15, 18391846.
  • 122
    Di Cristofano, A., Pesce, B., Cordon-Cardo, C., and Pandolfi, P. P. (1998) Pten is essential for embryonic development and tumour suppression. Nat. Genet. 19, 348355.
  • 123
    Lee, J. O., Yang, H., Georgescu, M. M., Di Cristofano, A., Maehama, T., et al. (1999) Crystal structure of the PTEN tumor suppressor: implications for its phosphoinositide phosphatase activity and membrane association. Cell 99, 323334.
  • 124
    Mao, M., Sudhahar, V., Ansenberger-Fricano, K., Fernandes, D. C., Tanaka, L. Y., et al. (2012) Nitroglycerin drives endothelial nitric oxide synthase activation via the phosphatidylinositol 3-kinase/protein kinase B pathway. Free Radic. Biol. Med. 52, 427435.
  • 125
    Ravi, Y., Selvendiran, K., Naidu, S. K., Meduru, S., Citro, L. A., et al. (2013) Pulmonary hypertension secondary to left-heart failure involves peroxynitrite-induced downregulation of PTEN in the lung. Hypertension 61, 593601.
  • 126
    Lee, S. R., Yang, K. S., Kwon, J., Lee, C., Jeong, W., et al. (2002) Reversible inactivation of the tumor suppressor PTEN by H2O2. J. Biol. Chem. 277, 2033620342.
  • 127
    Delgado-Esteban, M., Martin-Zanca, D., Andres-Martin, L., Almeida, A., and Bolanos, J. P. (2007) Inhibition of PTEN by peroxynitrite activates the phosphoinositide-3-kinase/Akt neuroprotective signaling pathway. J. Neurochem. 102, 194205.
  • 128
    Xue, B., Pulinilkunnil, T., Murano, I., Bence, K. K., He, H., et al. (2009) Neuronal protein tyrosine phosphatase 1B deficiency results in inhibition of hypothalamic AMPK and isoform-specific activation of AMPK in peripheral tissues. Mol. Cell. Biol. 29, 45634573.
  • 129
    Julien, S. G., Dube, N., Read, M., Penney, J., Paquet, M., et al. (2007) Protein tyrosine phosphatase 1B deficiency or inhibition delays ErbB2-induced mammary tumorigenesis and protects from lung metastasis. Nat. Genet. 39, 338346.
  • 130
    Nakamura, Y., Patrushev, N., Inomata, H., Mehta, D., Urao, N., et al. (2008) Role of protein tyrosine phosphatase 1B in vascular endothelial growth factor signaling and cell-cell adhesions in endothelial cells. Circ. Res. 102, 11821191.
  • 131
    Burdisso, J. E., Gonzalez, A., and Arregui, C. O. (2013) PTP1B promotes focal complex maturation, lamellar persistence and directional migration. J. Cell. Sci. 126, 18201831.
  • 132
    Ravichandran, L. V., Chen, H., Li, Y., and Quon, M. J. (2001) Phosphorylation of PTP1B at Ser(50) by Akt impairs its ability to dephosphorylate the insulin receptor. Mol. Endocrinol. 15, 17681780.
  • 133
    Ropelle, E. R., Pauli, J. R., Prada, P. O., de Souza, C. T., Picardi, P. K., et al. (2006) Reversal of diet-induced insulin resistance with a single bout of exercise in the rat: the role of PTP1B and IRS-1 serine phosphorylation. J. Physiol. 577, 9971007.
  • 134
    Mobasher, M. A., Gonzalez-Rodriguez, A., Santamaria, B., Ramos, S., Martin, M. A., et al. (2013) Protein tyrosine phosphatase 1B modulates GSK3beta/Nrf2 and IGFIR signaling pathways in acetaminophen-induced hepatotoxicity. Cell Death Dis. 4, e626.
  • 135
    Salmeen, A. and Barford, D. (2005) Functions and mechanisms of redox regulation of cysteine-based phosphatases. Antioxid. Redox Signal. 7, 560577.
  • 136
    Chen, Y. Y., Chu, H. M., Pan, K. T., Teng, C. H., Wang, D. L., et al. (2008) Cysteine S-nitrosylation protects protein-tyrosine phosphatase 1B against oxidation-induced permanent inactivation. J. Biol. Chem. 283, 3526535272.
  • 137
    Schoneich, C. (2005) Methionine oxidation by reactive oxygen species: reaction mechanisms and relevance to Alzheimer's disease. Biochim. Biophys. Acta 1703, 111119.
  • 138
    De Luca, A., Sanna, F., Sallese, M., Ruggiero, C., Grossi, M., et al. (2010) Methionine sulfoxide reductase A down-regulation in human breast cancer cells results in a more aggressive phenotype. Proc. Natl. Acad. Sci. USA 107, 1862818633.
  • 139
    Erickson, J. R., Joiner, M. L., Guan, X., Kutschke, W., Yang, J., et al. (2008) A dynamic pathway for calcium-independent activation of CaMKII by methionine oxidation. Cell 133, 462474.
  • 140
    Purohit, A., Rokita, A. G., Guan, X., Chen, B., Koval, O. M., et al. (2013) Oxidized Ca(2+)/calmodulin-dependent protein kinase II triggers atrial fibrillation. Circulation 128, 17481757.
  • 141
    Luo, M. and Anderson, M. E. (2013) Mechanisms of altered Ca(2)(+) handling in heart failure. Circ. Res. 113, 690708.
  • 142
    Luo, M., Guan, X., Luczak, E. D., Lang, D., Kutschke, W., et al. (2013) Diabetes increases mortality after myocardial infarction by oxidizing CaMKII. J. Clin. Invest. 123, 12621274.
  • 143
    Ansenberger-Fricano, K. A., Hart, P.C., Mao, M., Ganini, D., Baig, M.S., et al. (In review) MnSOD/SOD2 upregulation facilitates the metabolic reprogramming to glycolysis in cancer via AMPK signaling. submitted.
  • 144
    Kim, H. Y. and Gladyshev, V. N. (2007) Methionine sulfoxide reductases: selenoprotein forms and roles in antioxidant protein repair in mammals. Biochem. J. 407, 321329.
  • 145
    Glaser, C. B., Yamin, G., Uversky, V. N., and Fink, A. L. (2005) Methionine oxidation, alpha-synuclein and Parkinson's disease. Biochim. Biophys. Acta 1703, 157169.
  • 146
    Fink, A. L. (2006) The aggregation and fibrillation of alpha-synuclein. Acc. Chem. Res. 39, 628634.
  • 147
    Oien, D. B., Carrasco, G. A., and Moskovitz, J. (2011) Decreased phosphorylation and increased methionine oxidation of alpha-synuclein in the methionine sulfoxide reductase A knockout mouse. J. Amino Acids 2011, 721094.
  • 148
    Monteiro, G., Horta, B. B., Pimenta, D. C., Augusto, O., and Netto, L. E. (2007) Reduction of 1-Cys peroxiredoxins by ascorbate changes the thiol-specific antioxidant paradigm, revealing another function of vitamin C. Proc. Natl. Acad. Sci. USA 104, 48864891.
  • 149
    Jeon, S. M., Chandel, N. S., and Hay, N. (2012) AMPK regulates NADPH homeostasis to promote tumour cell survival during energy stress. Nature 485, 661665.
  • 150
    Cerutti, P. A. and Trump, B. F. (1991) Inflammation and oxidative stress in carcinogenesis. Cancer Cells 3, 17.
  • 151
    Toyokuni, S., Okamoto, K., Yodoi, J., and Hiai, H. (1995) Persistent oxidative stress in cancer. FEBS Lett. 358, 13.
  • 152
    Janssen, Y. M., Van Houten, B., Borm, P. J., and Mossman, B. T. (1993) Cell and tissue responses to oxidative damage. Lab. Invest. 69, 261274.
  • 153
    Finley, L. W. and Haigis, M. C. (2012) Metabolic regulation by SIRT3: implications for tumorigenesis. Trends Mol. Med. 18, 516523.
  • 154
    Bonini, M. G. and Gantner, B. N. (2013) The multifaceted activities of AMPK in tumor progression-why the “one size fits all” definition does not fit at all? IUBMB Life 65, 889896.
  • 155
    Coller, H. A. (2013) Is cancer a metabolic disease? Am. J. Pathol 184, 417.
  • 156
    Belardi, V., Gallagher, E. J., Novosyadlyy, R., and Leroith, D. (2013) Insulin and IGFs in obesity-related breast cancer. J. Mammary Gland Biol. Neoplasia 18, 277289.
  • 157
    Gallagher, E. J., Alikhani, N., Tobin-Hess, A., Blank, J., Buffin, N. J., et al. (2013) Insulin receptor phosphorylation by endogenous insulin or the insulin analog AspB10 promotes mammary tumor growth independent of the IGF-I receptor. Diabetes 62, 35533560.
  • 158
    Santos, C. X., Bonini, M. G., and Augusto, O. (2000) Role of the carbonate radical anion in tyrosine nitration and hydroxylation by peroxynitrite. Arch. Biochem. Biophys. 377, 146152.
  • 159
    Alvarez, B. and Radi, R. (2003) Peroxynitrite reactivity with amino acids and proteins. Amino Acids 25, 295311.
  • 160
    Pfeiffer, S., Lass, A., Schmidt, K., and Mayer, B. (2001) Protein tyrosine nitration in mouse peritoneal macrophages activated in vitro and in vivo: evidence against an essential role of peroxynitrite. FASEB J. 15, 23552364.
  • 161
    Pfeiffer, S., Lass, A., Schmidt, K., and Mayer, B. (2001) Protein tyrosine nitration in cytokine-activated murine macrophages. Involvement of a peroxidase/nitrite pathway rather than peroxynitrite. J. Biol. Chem. 276, 3405134058.
  • 162
    Nakai, K. and Mason, R. P. (2005) Immunochemical detection of nitric oxide and nitrogen dioxide trapping of the tyrosyl radical and the resulting nitrotyrosine in sperm whale myoglobin. Free Radic. Biol. Med. 39, 10501058.
  • 163
    Chen, Y. R., Chen, C. L., Chen, W., Zweier, J. L., Augusto, O., et al. (2004) Formation of protein tyrosine ortho-semiquinone radical and nitrotyrosine from cytochrome c-derived tyrosyl radical. J. Biol. Chem. 279, 1805418062.
  • 164
    Gunther, M. R., Hsi, L. C., Curtis, J. F., Gierse, J. K., Marnett, L. J., et al. (1997) Nitric oxide trapping of the tyrosyl radical of prostaglandin H synthase-2 leads to tyrosine iminoxyl radical and nitrotyrosine formation. J. Biol. Chem. 272, 1708617090.
  • 165
    MacMillan-Crow, L. A. and Thompson, J. A. (1999) Tyrosine modifications and inactivation of active site manganese superoxide dismutase mutant (Y34F) by peroxynitrite. Arch. Biochem. Biophys. 366, 8288.
  • 166
    Moreno, D. M., Marti, M. A., De Biase, P. M., Estrin, D. A., Demicheli, V., et al. (2011) Exploring the molecular basis of human manganese superoxide dismutase inactivation mediated by tyrosine 34 nitration. Arch. Biochem. Biophys. 507, 304309.
  • 167
    Rodriguez-Roldan, V., Garcia-Heredia, J. M., Navarro, J. A., De la Rosa, M. A., and Hervas, M. (2008) Effect of nitration on the physicochemical and kinetic features of wild-type and monotyrosine mutants of human respiratory cytochrome c. Biochemistry 47, 1237112379.
  • 168
    Garcia-Heredia, J. M., Diaz-Moreno, I., Diaz-Quintana, A., Orzaez, M., Navarro, J. A., et al. (2012) Specific nitration of tyrosines 46 and 48 makes cytochrome c assemble a non-functional apoptosome. FEBS Lett. 586, 154158.
  • 169
    Jang, B. and Han, S. (2006) Biochemical properties of cytochrome c nitrated by peroxynitrite. Biochimie 88, 5358.
  • 170
    Bartesaghi, S., Wenzel, J., Trujillo, M., Lopez, M., Joseph, J., et al. (2010) Lipid peroxyl radicals mediate tyrosine dimerization and nitration in membranes. Chem. Res. Toxicol. 23, 821835.
  • 171
    Bartesaghi, S., Peluffo, G., Zhang, H., Joseph, J., Kalyanaraman, B., et al. (2008) Tyrosine nitration, dimerization, and hydroxylation by peroxynitrite in membranes as studied by the hydrophobic probe N-t-BOC-l-tyrosine tert-butyl ester. Methods Enzymol. 441, 217236.
  • 172
    Bartesaghi, S., Ferrer-Sueta, G., Peluffo, G., Valez, V., Zhang, H., et al. (2007) Protein tyrosine nitration in hydrophilic and hydrophobic environments. Amino Acids 32, 501515.
  • 173
    Zhang, H., Zielonka, J., Sikora, A., Joseph, J., Xu, Y., et al. (2009) The effect of neighboring methionine residue on tyrosine nitration and oxidation in peptides treated with MPO, H2O2, and NO2(-) or peroxynitrite and bicarbonate: role of intramolecular electron transfer mechanism? Arch. Biochem. Biophys. 484, 134145.
  • 174
    Zhang, H., Xu, Y., Joseph, J., and Kalyanaraman, B. (2005) Intramolecular electron transfer between tyrosyl radical and cysteine residue inhibits tyrosine nitration and induces thiyl radical formation in model peptides treated with myeloperoxidase, H2O2, and NO2-: EPR SPIN trapping studies. J. Biol. Chem. 280, 4068440698.
  • 175
    Zhang, H., Joseph, J., Feix, J., Hogg, N., and Kalyanaraman, B. (2001) Nitration and oxidation of a hydrophobic tyrosine probe by peroxynitrite in membranes: comparison with nitration and oxidation of tyrosine by peroxynitrite in aqueous solution. Biochemistry 40, 76757686.
  • 176
    Mallozzi, C., D'Amore, C., Camerini, S., Macchia, G., Crescenzi, M., et al. (2013) Phosphorylation and nitration of tyrosine residues affect functional properties of Synaptophysin and Dynamin, I., two proteins involved in exo-endocytosis of synaptic vesicles. Biochim. Biophys. Acta 1833, 110121.
  • 177
    Pilon, G., Charbonneau, A., White, P. J., Dallaire, P., Perreault, M., et al. (2010) Endotoxin mediated-iNOS induction causes insulin resistance via ONOO(-) induced tyrosine nitration of IRS-1 in skeletal muscle. PLoS One 5, e15912.
  • 178
    Yakovlev, V. A., Bayden, A. S., Graves, P. R., Kellogg, G. E., and Mikkelsen, R. B. (2010) Nitration of the tumor suppressor protein p53 at tyrosine 327 promotes p53 oligomerization and activation. Biochemistry 49, 53315339.
  • 179
    Csibi, A., Communi, D., Muller, N., and Bottari, S. P. (2010) Angiotensin II inhibits insulin-stimulated GLUT4 translocation and Akt activation through tyrosine nitration-dependent mechanisms. PLoS One 5, e10070.
  • 180
    Winterbourn, C. C. and Kettle, A. J. (2000) Biomarkers of myeloperoxidase-derived hypochlorous acid. Free Radic. Biol. Med. 29, 403409.
  • 181
    Talib, J., Pattison, D. I., Harmer, J. A., Celermajer, D. S., and Davies, M. J. (2012) High plasma thiocyanate levels modulate protein damage induced by myeloperoxidase and perturb measurement of 3-chlorotyrosine. Free Radic. Biol. Med. 53, 2029.
  • 182
    Wu, W., Samoszuk, M. K., Comhair, S. A., Thomassen, M. J., Farver, C. F., et al. (2000) Eosinophils generate brominating oxidants in allergen-induced asthma. J. Clin. Invest. 105, 14551463.
  • 183
    Thomson, E., Brennan, S., Senthilmohan, R., Gangell, C. L., Chapman, A. L., et al. (2010) Identifying peroxidases and their oxidants in the early pathology of cystic fibrosis. Free Radic. Biol. Med. 49, 13541360.
  • 184
    Winterbourn, C. C. (2002) Biological reactivity and biomarkers of the neutrophil oxidant, hypochlorous acid. Toxicology 181–182, 223227.
  • 185
    Linares, E., Giorgio, S., Mortara, R. A., Santos, C. X., Yamada, A. T., et al. (2001) Role of peroxynitrite in macrophage microbicidal mechanisms in vivo revealed by protein nitration and hydroxylation. Free Radic. Biol. Med. 30, 12341242.
  • 186
    Simpson, J. A., Gieseg, S. P., and Dean, R. T. (1993) Free radical and enzymatic mechanisms for the generation of protein bound reducing moieties. Biochim. Biophys. Acta 1156, 190196.
  • 187
    Morin, B., Davies, M. J., and Dean, R. T. (1998) The protein oxidation product 3,4-dihydroxyphenylalanine (DOPA) mediates oxidative DNA damage. Biochem. J. 330 (Pt 3), 10591067.
  • 188
    Gieseg, S. P., Simpson, J. A., Charlton, T. S., Duncan, M. W., and Dean, R. T. (1993) Protein-bound 3,4-dihydroxyphenylalanine is a major reductant formed during hydroxyl radical damage to proteins. Biochemistry 32, 47804786.
  • 189
    Koppenol, W. H. (2001) The Haber-Weiss cycle—70 years later. Redox Rep. 6, 229234.
  • 190
    Batthyany, C., Santos, C. X., Botti, H., Cervenansky, C., Radi, R., et al. (2000) Direct evidence for apo B-100-mediated copper reduction: studies with purified apo B-100 and detection of tryptophanyl radicals. Arch. Biochem. Biophys. 384, 335340.
  • 191
    Medinas, D. B., Gozzo, F. C., Santos, L. F., Iglesias, A. H., and Augusto, O. (2010) A ditryptophan cross-link is responsible for the covalent dimerization of human superoxide dismutase 1 during its bicarbonate-dependent peroxidase activity. Free Radic. Biol. Med. 49, 10461053.
  • 192
    Samhan-Arias, A. K., Tyurina, Y. Y., and Kagan, V. E. (2011) Lipid antioxidants: free radical scavenging versus regulation of enzymatic lipid peroxidation. J. Clin. Biochem. Nutr. 48, 9195.
  • 193
    Huang, Z., Jiang, J., Belikova, N. A., Stoyanovsky, D. A., Kagan, V. E., et al. (2010) Protection of normal brain cells from gamma-irradiation-induced apoptosis by a mitochondria-targeted triphenyl-phosphonium-nitroxide: a possible utility in glioblastoma therapy. J. Neurooncol. 100, 18.
  • 194
    Jin, H., Kanthasamy, A., Ghosh, A., Anantharam, V., Kalyanaraman, B., et al. (2013) Mitochondria-targeted antioxidants for treatment of Parkinson's disease: preclinical and clinical outcomes. Biochim. Biophys. Acta.
  • 195
    Dilip, A., Cheng, G., Joseph, J., Kunnimalaiyaan, S., Kalyanaraman, B., et al. (2013) Mitochondria-targeted antioxidant and glycolysis inhibition: synergistic therapy in hepatocellular carcinoma. Anticancer Drugs 24, 881888.
  • 196
    Cheng, G., Zielonka, J., McAllister, D. M., Mackinnon, A. C., Jr., Joseph, J., et al. (2013) Mitochondria-targeted vitamin E analogs inhibit breast cancer cell energy metabolism and promote cell death. BMC Cancer 13, 285.
  • 197
    Sovari, A. A., Rutledge, C. A., Jeong, E. M., Dolmatova, E., Arasu, D., et al. (2013) Mitochondria oxidative stress, connexin43 remodeling, and sudden arrhythmic death. Circ. Arrhythm. Electrophysiol. 6, 623631.
  • 198
    Sieracki, N. A., Gantner, B. N., Mao, M., Horner, J. H., Ye, R. D., et al. (2013) Bioluminescent detection of peroxynitrite with a boronic acid-caged luciferin. Free Radic. Biol. Med. 61C, 4050.