Skip to main content
SpringerLink
Log in

Fluorescent Imaging of Redox Species in Multicellular Organisms

  • Chapter
  • First Online:
Oxidative Stress and Redox Regulation

Abstract

Redox processes play a crucial role in many aspects of physiology and changes in cellular redox species are increasingly being linked to a wide range of pathological conditions. Redox species can change dynamically at the subcellular compartment-, cell- and tissue-level and different redox species likely convey different biological information. The investigation of redox biology in a living multicellular organism is particularly difficult and is hampered by the lack of tools which offer redox species specificity and the necessary spatial and temporal resolution. In recent years there has been intense development of small organic chemical and genetically encoded fluorescent probes which have vastly improved our ability to investigate cellular redox processes. In this chapter we describe the currently available fluorescent probes, focusing in particular on those which have already been applied to multicellular organisms or those which we believe have the potential for in vivo use in the future. We discuss advantages and disadvantages of the different kinds of probes and highlight their major problems and limitations.

The authors Yuuta Fujikawa and Bruce Morgan contributed equally

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

Access this chapter

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

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abo M, Urano Y, Hanaoka K, Terai T, Komatsu T, Nagano T (2011) Development of a highly sensitive fluorescence probe for hydrogen peroxide. J Am Chem Soc 133:10629–10637

    CAS  PubMed  Google Scholar 

  • Albers AE, Okreglak VS, Chang CJ (2006) A FRET-based approach to ratiometric fluorescence detection of hydrogen peroxide. J Am Chem Soc 128:9640–9641

    CAS  PubMed  Google Scholar 

  • Albers AE, Dickinson BC, Miller EW, Chang CJ (2008) A red-emitting naphthofluorescein-based fluorescent probe for selective detection of hydrogen peroxide in living cells. Bioorg Med Chem Lett 18:5948–5950

    CAS  PubMed Central  PubMed  Google Scholar 

  • Albrecht SC, Barata AG, Grosshans J, Teleman AA, Dick TP (2011) In vivo mapping of hydrogen peroxide and oxidized glutathione reveals chemical and regional specificity of redox homeostasis. Cell Metab 14:819–829

    CAS  PubMed  Google Scholar 

  • Atkuri KR, Herzenberg LA, Niemi AK, Cowan T (2007) Importance of culturing primary lymphocytes at physiological oxygen levels. Proc Natl Acad Sci USA 104:4547–4552

    CAS  PubMed  Google Scholar 

  • Back P, de Vos WH, Depuydt GG, Matthijssens F, Vanfleteren JR, Braeckman BP (2011) Exploring real-time in vivo redox biology of developing and aging Caenorhabditis eleganse. Free Radic Biol Med 52(5):850–859

    PubMed  Google Scholar 

  • Belousov VV, Fradkov AF, Lukyanov KA, Staroverov DB, Shakhbazov KS, Terskikh AV, Lukyanov S (2006) Genetically encoded fluorescent indicator for intracellular hydrogen peroxide. Nat Methods 3:281–286

    CAS  PubMed  Google Scholar 

  • Benov L, Sztejnberg L, Fridovich I (1998) Critical evaluation of the use of hydroethidine as a measure of superoxide anion radical. Free Radic Biol Med 25:826–831

    CAS  PubMed  Google Scholar 

  • Bernal PJ, Leelavanichkul K, Bauer E, Cao R, Wilson A, Wasserloos KJ, Watkins SC, Pitt BR, St Croix CM (2008) Nitric-oxide-mediated zinc release contributes to hypoxic regulation of pulmonary vascular tone. Circ Res 102:1575–1583

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bjornberg O, Ostergaard H, Winther JR (2006a) Measuring intracellular redox conditions using GFP-based sensors. Antioxid Redox Signal 8:354–361

    PubMed  Google Scholar 

  • Bjornberg O, Ostergaard H, Winther JR (2006b) Mechanistic insight provided by glutaredoxin within a fusion to redox-sensitive yellow fluorescent protein. Biochemistry 45:2362–2371

    PubMed  Google Scholar 

  • Boghossian AA, Zhang J, Barone PW, Reuel NF, Kim JH, Heller DA, Ahn JH, Hilmer AJ, Rwei A, Arkalgud JR, Zhang CT, Strano MS (2011) Near-infrared fluorescent sensors based on single-walled carbon nanotubes for life sciences applications. ChemSusChem 4:848–863

    CAS  PubMed  Google Scholar 

  • Buxser SE, Sawada G, Raub TJ (1999) Analytical and numerical techniques for evaluation of free radical damage in cultured cells using imaging cytometry and fluorescent indicators. Methods Enzymol 300:256–275

    CAS  PubMed  Google Scholar 

  • Cabreiro F, Ackerman D, Doonan R, Araiz C, Back P, Papp D, Braeckman BP, Gems D (2011) Increased life span from overexpression of superoxide dismutase in Caenorhabditis elegans is not caused by decreased oxidative damage. Free Radic Biol Med 51:1575–1582

    CAS  PubMed Central  PubMed  Google Scholar 

  • Casanova D, Bouzigues C, Nguyen TL, Ramodiharilafy RO, Bouzhir-Sima L, Gacoin T, Boilot JP, Tharaux PL, Alexandrou A (2009) Single europium-doped nanoparticles measure temporal pattern of reactive oxygen species production inside cells. Nat Nanotechnol 4:581–585

    CAS  PubMed  Google Scholar 

  • Chen X, Zhou Y, Peng X, Yoon J (2010) Fluorescent and colorimetric probes for detection of thiols. Chem Soc Rev 39:2120–2135

    CAS  PubMed  Google Scholar 

  • Chen X, Tian X, Shin I, Yoon J (2011) Fluorescent and luminescent probes for detection of reactive oxygen and nitrogen species. Chem Soc Rev 40:4783–4804

    CAS  PubMed  Google Scholar 

  • Cook JA, Iype SN, Mitchell JB (1991) Differential specificity of monochlorobimane for isozymes of human and rodent glutathione S-transferases. Cancer Res 51:1606–1612

    CAS  PubMed  Google Scholar 

  • Costa A, Drago I, Behera S, Zottini M, Pizzo P, Schroeder JI, Pozzan T, Lo Schiavo F (2010) H2O2 in plant peroxisomes: an in vivo analysis uncovers a Ca2+-dependent scavenging system. Plant J 62:760–772

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dalle-Donne I, Rossi R, Colombo G, Giustarini D, Milzani A (2009) Protein S-glutathionylation: a regulatory device from bacteria to humans. Trends Biochem Sci 34:85–96

    CAS  PubMed  Google Scholar 

  • de Souza N (2007) Too much of a good thing. Nat Methods 4:386

    PubMed  Google Scholar 

  • Delaunay A, Pflieger D, Barrault MB, Vinh J, Toledano MB (2002) A thiol peroxidase is an H2O2 receptor and redox-transducer in gene activation. Cell 111:471–481

    CAS  PubMed  Google Scholar 

  • Delic M, Mattanovich D, Gasser B (2010) Monitoring intracellular redox conditions in the endoplasmic reticulum of living yeasts. FEMS Microbiol Lett 306:61–66

    CAS  PubMed  Google Scholar 

  • Dickinson BC, Chang CJ (2008) A targetable fluorescent probe for imaging hydrogen peroxide in the mitochondria of living cells. J Am Chem Soc 130:9638–9639

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dickinson BC, Chang CJ (2011) Chemistry and biology of reactive oxygen species in signaling or stress responses. Nat Chem Biol 7:504–511

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dickinson BC, Huynh C, Chang CJ (2010) A palette of fluorescent probes with varying emission colors for imaging hydrogen peroxide signaling in living cells. J Am Chem Soc 132:5906–5915

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dickinson BC, Peltier J, Stone D, Schaffer DV, Chang CJ (2011a) Nox2 redox signaling maintains essential cell populations in the brain. Nat Chem Biol 7:106–112

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dickinson BC, Tang Y, Chang Z, Chang CJ (2011b) A nuclear-localized fluorescent hydrogen peroxide probe for monitoring sirtuin-mediated oxidative stress responses in vivo. Chem Biol 18:943–948

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dooley CT, Dore TM, Hanson GT, Jackson WC, Remington SJ, Tsien RY (2004) Imaging dynamic redox changes in mammalian cells with green fluorescent protein indicators. J Biol Chem 279:22284–22293

    CAS  PubMed  Google Scholar 

  • Drummond GR, Selemidis S, Griendling KK, Sobey CG (2011) Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets. Nat Rev Drug Discov 10:453–471

    CAS  PubMed Central  PubMed  Google Scholar 

  • Grant CM, Maciver FH, Dawes IW (1996) Glutathione is an essential metabolite required for resistance to oxidative stress in the yeast Saccharomyces cerevisiae. Curr Genet 29:511–515

    CAS  PubMed  Google Scholar 

  • Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell 140: 883–899

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gutscher M, Pauleau AL, Marty L, Brach T, Wabnitz GH, Samstag Y, Meyer AJ, Dick TP (2008) Real-time imaging of the intracellular glutathione redox potential. Nat Methods 5:553–559

    CAS  PubMed  Google Scholar 

  • Gutscher M, Sobotta MC, Wabnitz GH, Ballikaya S, Meyer AJ, Samstag Y, Dick TP (2009) Proximity-based protein thiol oxidation by H2O2-scavenging peroxidases. J Biol Chem 284:31532–31540

    CAS  PubMed  Google Scholar 

  • Guzman JN, Sanchez-Padilla J, Wokosin D, Kondapalli J, Ilijic E, Schumacker PT, Surmeier DJ (2010) Oxidant stress evoked by pacemaking in dopaminergic neurons is attenuated by DJ-1. Nature 468:696–700

    CAS  PubMed  Google Scholar 

  • Haga S, Remington SJ, Morita N, Terui K, Ozaki M (2009) Hepatic ischemia induced immediate oxidative stress after reperfusion and determined the severity of the reperfusion-induced damage. Antioxid Redox Signal 11:2563–2572

    CAS  PubMed  Google Scholar 

  • Halliwell B, Whiteman M (2004) Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean? Br J Pharmacol 142:231–255

    CAS  PubMed  Google Scholar 

  • Hanson GT, Aggeler R, Oglesbee D, Cannon M, Capaldi RA, Tsien RY, Remington SJ (2004) Investigating mitochondrial redox potential with redox-sensitive green fluorescent protein indicators. J Biol Chem 279:13044–13053

    CAS  PubMed  Google Scholar 

  • Harding HP, Zhang Y, Zeng H, Novoa I, Lu PD, Calfon M, Sadri N, Yun C, Popko B, Paules R, Stojdl DF, Bell JC, Hettmann T, Leiden JM, Ron D (2003) An integrated stress response regulates amino acid metabolism and resistance to oxidative stress. Mol Cell 11:619–633

    CAS  PubMed  Google Scholar 

  • Harrison DG, Guzik TJ, Lob HE, Madhur MS, Marvar PJ, Thabet SR, Vinh A, Weyand CM (2011) Inflammation, immunity, and hypertension. Hypertension 57:132–140

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hempel SL, Buettner GR, O’Malley YQ, Wessels DA, Flaherty DM (1999) Dihydrofluorescein diacetate is superior for detecting intracellular oxidants: comparison with 2′,7′-dichlorodihydrofluorescein diacetate, 5(and 6)-carboxy-2′,7′-dichlorodihydrofluorescein diacetate, and dihydrorhodamine 123. Free Radic Biol Med 27:146–159

    CAS  PubMed  Google Scholar 

  • Hess DT, Stamler JS (2012) Regulation by S-nitrosylation of protein posttranslational modification. J Biol Chem 287(7):4411–4418

    Google Scholar 

  • Huai-Yun H, Secrest DT, Mark KS, Carney D, Brandquist C, Elmquist WF, Miller DW (1998) Expression of multidrug resistance-associated protein (MRP) in brain microvessel endothelial cells. Biochem Biophys Res Commun 243:816–820

    CAS  PubMed  Google Scholar 

  • Huang Z, Zhang W, Fang H, Zheng M, Wang X, Xu J, Cheng H, Gong G, Wang W, Dirksen RT, Sheu SS (2011) Response to “A critical evaluation of cpYFP as a probe for superoxide”. Free Radic Biol Med 51:1937–1940

    CAS  PubMed  Google Scholar 

  • Hung YP, Albeck JG, Tantama M, Yellen G (2011) Imaging cytosolic NADH-NAD(+) redox state with a genetically encoded fluorescent biosensor. Cell Metab 14:545–554

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ignarro LJ, Fukuto JM, Griscavage JM, Rogers NE, Byrns RE (1993) Oxidation of nitric oxide in aqueous solution to nitrite but not nitrate: comparison with enzymatically formed nitric oxide from L-arginine. Proc Natl Acad Sci USA 90:8103–8107

    CAS  PubMed  Google Scholar 

  • Imura T, Kanatani S, Fukuda S, Miyamoto Y, Hisatsune T (2005) Layer-specific production of nitric oxide during cortical circuit formation in postnatal mouse brain. Cereb Cortex 15: 332–340

    PubMed  Google Scholar 

  • Ishikawa T, Wright CD, Ishizuka H (1994) GS-X pump is functionally overexpressed in cis-diamminedichloroplatinum (II)-resistant human leukemia HL-60 cells and down-regulated by cell-differentiation. J Biol Chem 269:29085–29093

    CAS  PubMed  Google Scholar 

  • Izumi S, Urano Y, Hanaoka K, Terai T, Nagano T (2009) A simple and effective strategy to increase the sensitivity of fluorescence probes in living cells. J Am Chem Soc 131:10189–10200

    CAS  PubMed  Google Scholar 

  • Jakob U, Muse W, Eser M, Bardwell JC (1999) Chaperone activity with a redox switch. Cell 96:341–352

    CAS  PubMed  Google Scholar 

  • Jiang K, Schwarzer C, Lally E, Zhang S, Ruzin S, Machen T, Remington SJ, Feldman L (2006) Expression and characterization of a redox-sensing green fluorescent protein (reduction-oxidation-sensitive green fluorescent protein) in Arabidopsis. Plant Physiol 141:397–403

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jin H, Heller DA, Kalbacova M, Kim JH, Zhang J, Boghossian AA, Maheshri N, Strano MS (2010) Detection of single-molecule H2O2 signalling from epidermal growth factor receptor using fluorescent single-walled carbon nanotubes. Nat Nanotechnol 5:302–309

    CAS  PubMed  Google Scholar 

  • Johnson D, Nehrke K (2010) Mitochondrial fragmentation leads to intracellular acidification in Caenorhabditis elegans and mammalian cells. Mol Biol Cell 21:2191–2201

    CAS  PubMed Central  PubMed  Google Scholar 

  • Johnson LV, Walsh ML, Bockus BJ, Chen LB (1981) Monitoring of relative mitochondrial membrane potential in living cells by fluorescence microscopy. J Cell Biol 88:526–535

    CAS  PubMed  Google Scholar 

  • Jubany-Mari T, Alegre-Batlle L, Jiang K, Feldman LJ (2010) Use of a redox-sensing GFP (c-roGFP1) for real-time monitoring of cytosol redox status in Arabidopsis thaliana water-stressed plants. FEBS Lett 584:889–897

    CAS  PubMed  Google Scholar 

  • Karton-Lifshin N, Segal E, Omer L, Portnoy M, Satchi-Fainaro R, Shabat D (2011) A unique paradigm for a Turn-ON near-infrared cyanine-based probe: noninvasive intravital optical imaging of hydrogen peroxide. J Am Chem Soc 133:10960–10965

    CAS  PubMed  Google Scholar 

  • Keelan J, Allen NJ, Antcliffe D, Pal S, Duchen MR (2001) Quantitative imaging of glutathione in hippocampal neurons and glia in culture using monochlorobimane. J Neurosci Res 66:873–884

    CAS  PubMed  Google Scholar 

  • Kenmoku S, Urano Y, Kojima H, Nagano T (2007) Development of a highly specific rhodamine-based fluorescence probe for hypochlorous acid and its application to real-time imaging of phagocytosis. J Am Chem Soc 129:7313–7318

    CAS  PubMed  Google Scholar 

  • Kishi S, Bayliss PE, Uchiyama J, Koshimizu E, Qi J, Nanjappa P, Imamura S, Islam A, Neuberg D, Amsterdam A, Roberts TM (2008) The identification of zebrafish mutants showing alterations in senescence-associated biomarkers. PLOS Genet 4:e1000152

    PubMed Central  PubMed  Google Scholar 

  • Klohs J, Wunder A, Licha K (2008) Near-infrared fluorescent probes for imaging vascular pathophysiology. Basic Res Cardiol 103:144–151

    CAS  PubMed  Google Scholar 

  • Koide Y, Urano Y, Kenmoku S, Kojima H, Nagano T (2007) Design and synthesis of fluorescent probes for selective detection of highly reactive oxygen species in mitochondria of living cells. J Am Chem Soc 129:10324–10325

    CAS  PubMed  Google Scholar 

  • Koide Y, Urano Y, Hanaoka K, Terai T, Nagano T (2011) Development of an Si-rhodamine-based far-red to near-infrared fluorescence probe selective for hypochlorous acid and its applications for biological imaging. J Am Chem Soc 133:5680–5682

    CAS  PubMed  Google Scholar 

  • Kojima H, Nakatsubo N, Kikuchi K, Kawahara S, Kirino Y, Nagoshi H, Hirata Y, Nagano T (1998a) Detection and imaging of nitric oxide with novel fluorescent indicators: diaminofluoresceins. Anal Chem 70:2446–2453

    CAS  PubMed  Google Scholar 

  • Kojima H, Nakatsubo N, Kikuchi K, Urano Y, Higuchi T, Tanaka J, Kudo Y, Nagano T (1998b) Direct evidence of NO production in rat hippocampus and cortex using a new fluorescent indicator: DAF-2 DA. Neuroreport 9:3345–3348

    CAS  PubMed  Google Scholar 

  • Kojima H, Sakurai K, Kikuchi K, Kawahara S, Kirino Y, Nagoshi H, Hirata Y, Nagano T (1998c) Development of a fluorescent indicator for nitric oxide based on the fluorescein chromophore. Chem Pharm Bull(Tokyo) 46:373–375

    CAS  Google Scholar 

  • Kojima H, Urano Y, Kikuchi K, Higuchi T, Hirata Y, Nagano T (1999) Fluorescent indicators for imaging nitric oxide production. Angew Chem Int Ed Engl 38:3209–3212

    CAS  PubMed  Google Scholar 

  • Kojima H, Hirotani M, Nakatsubo N, Kikuchi K, Urano Y, Higuchi T, Hirata Y, Nagano T (2001) Bioimaging of nitric oxide with fluorescent indicators based on the rhodamine chromophore. Anal Chem 73:1967–1973

    CAS  PubMed  Google Scholar 

  • Kolossov VL, Spring BQ, Sokolowski A, Conour JE, Clegg RM, Kenis PJ, Gaskins HR (2008) Engineering redox-sensitive linkers for genetically encoded FRET-based biosensors. Exp Biol Med (Maywood) 233:238–248

    CAS  Google Scholar 

  • Kolossov VL, Spring BQ, Clegg RM, Henry JJ, Sokolowski A, Kenis PJ, Gaskins HR (2011) Development of a high-dynamic range, GFP-based FRET probe sensitive to oxidative microenvironments. Exp Biol Med (Maywood) 236:681–691

    CAS  PubMed Central  Google Scholar 

  • Kundu K, Knight SF, Willett N, Lee S, Taylor WR, Murthy N (2009) Hydrocyanines: a class of fluorescent sensors that can image reactive oxygen species in cell culture, tissue, and in vivo. Angew Chem Int Ed Engl 48:299–303

    CAS  PubMed  Google Scholar 

  • Lawrence A, Jones CM, Wardman P, Burkitt MJ (2003) Evidence for the role of a peroxidase compound I-type intermediate in the oxidation of glutathione, NADH, ascorbate, and dichlorofluorescin by cytochrome c/H2O2. Implications for oxidative stress during apoptosis. J Biol Chem 278:29410–29419

    CAS  PubMed  Google Scholar 

  • Lebel CP, Ischiropoulos H, Bondy SC (1992) Evaluation of the probe 2′,7′-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol 5: 227–231

    CAS  PubMed  Google Scholar 

  • Lee D, Khaja S, Velasquez-Castano JC, Dasari M, Sun C, Petros J, Taylor WR, Murthy N (2007) In vivo imaging of hydrogen peroxide with chemiluminescent nanoparticles. Nat Mater 6:765–769

    CAS  PubMed  Google Scholar 

  • Lepiller S, Laurens V, Bouchot A, Herbomel P, Solary E, Chluba J (2007) Imaging of nitric oxide in a living vertebrate using a diamino-fluorescein probe. Free Radic Biol Med 43:619–627

    CAS  PubMed  Google Scholar 

  • Lim MH, Xu D, Lippard SJ (2006) Visualization of nitric oxide in living cells by a copper-based fluorescent probe. Nat Chem Biol 2:375–380

    CAS  PubMed  Google Scholar 

  • Lohman JR, Remington SJ (2008) Development of a family of redox-sensitive green fluorescent protein indicators for use in relatively oxidizing subcellular environments. Biochemistry 47:8678–8688

    CAS  PubMed  Google Scholar 

  • Ludescher C, Thaler J, Drach D, Drach J, Spitaler M, Gattringer C, Huber H, Hofmann J (1992) Detection of activity of P-glycoprotein in human tumour samples using rhodamine 123. Br J Haematol 82:161–168

    CAS  PubMed  Google Scholar 

  • Maeda H, Yamamoto K, Kohno I, Hafsi L, Itoh N, Nakagawa S, Kanagawa N, Suzuki K, Uno T (2007) Design of a practical fluorescent probe for superoxide based on protection-deprotection chemistry of fluoresceins with benzenesulfonyl protecting groups. Chemistry 13:1946–1954

    CAS  PubMed  Google Scholar 

  • Markvicheva KN, Bilan DS, Mishina NM, Gorokhovatsky AY, Vinokurov LM, Lukyanov S, Belousov VV (2011) A genetically encoded sensor for H2O2 with expanded dynamic range. Bioorg Med Chem 19:1079–1084

    CAS  PubMed  Google Scholar 

  • Marty L, Siala W, Schwarzlander M, Fricker MD, Wirtz M, Sweetlove LJ, Meyer Y, Meyer AJ, Reichheld JP, Hell R (2009) The NADPH-dependent thioredoxin system constitutes a functional backup for cytosolic glutathione reductase in Arabidopsis. Proc Natl Acad Sci USA 106:9109–9114

    CAS  PubMed  Google Scholar 

  • Maughan SC, Pasternak M, Cairns N, Kiddle G, Brach T, Jarvis R, Haas F, Nieuwland J, Lim B, Muller C, Salcedo-Sora E, Kruse C, Orsel M, Hell R, Miller AJ, Bray P, Foyer CH, Murray JA, Meyer AJ, Cobbett CS (2010) Plant homologs of the Plasmodium falciparum chloroquine-resistance transporter, PfCRT, are required for glutathione homeostasis and stress responses. Proc Natl Acad Sci USA 107:2331–2336

    CAS  PubMed  Google Scholar 

  • McQuade LE, Ma J, Lowe G, Ghatpande A, Gelperin A, Lippard SJ (2010) Visualization of nitric oxide production in the mouse main olfactory bulb by a cell-trappable copper(II) fluorescent probe. Proc Natl Acad Sci USA 107:8525–8530

    CAS  PubMed  Google Scholar 

  • Meister A (1988) Glutathione metabolism and its selective modification. J Biol Chem 263: 17205–17208

    CAS  PubMed  Google Scholar 

  • Meyer AJ, Dick TP (2010) Fluorescent protein-based redox probes. Antioxid Redox Signal 13:621–650

    CAS  PubMed  Google Scholar 

  • Meyer AJ, Fricker MD (2000) Direct measurement of glutathione in epidermal cells of intact Arabidopsis roots by two-photon laser scanning microscopy. J Microsc Oxf 198:174–181

    CAS  Google Scholar 

  • Meyer AJ, May MJ, Fricker M (2001) Quantitative in vivo measurement of glutathione in Arabidopsis cells. Plant J 27:67–78

    CAS  PubMed  Google Scholar 

  • Meyer AJ, Brach T, Marty L, Kreye S, Rouhier N, Jacquot JP, Hell R (2007) Redox-sensitive GFP in Arabidopsis thaliana is a quantitative biosensor for the redox potential of the cellular glutathione redox buffer. Plant J 52:973–986

    CAS  PubMed  Google Scholar 

  • Mieyal JJ, Chock PB (2012) Posttranslational modification of cysteine in redox signaling and oxidative stress: focus on S-glutathionylation. Antioxid Redox Signal 16(6):471–475

    CAS  PubMed  Google Scholar 

  • Mieyal JJ, Gallogly MM, Qanungo S, Sabens EA, Shelton MD (2008) Molecular mechanisms and clinical implications of reversible protein S-glutathionylation. Antioxid Redox Signal 10: 1941–1988

    CAS  PubMed  Google Scholar 

  • Miller EW, Tulyathan O, Isacoff EY, Chang CJ (2007) Molecular imaging of hydrogen peroxide produced for cell signaling. Nat Chem Biol 3:263–267

    CAS  PubMed  Google Scholar 

  • Miyawaki A (2011) Development of probes for cellular functions using fluorescent proteins and fluorescence resonance energy transfer. Annu Rev Biochem 80:357–373

    CAS  PubMed  Google Scholar 

  • Morgan MJ, Lehmann M, Schwarzlander M, Baxter CJ, Sienkiewicz-Porzucek A, Williams TC, Schauer N, Fernie AR, Fricker MD, Ratcliffe RG, Sweetlove LJ, Finkemeier I (2008) Decrease in manganese superoxide dismutase leads to reduced root growth and affects tricarboxylic acid cycle flux and mitochondrial redox homeostasis. Plant Physiol 147:101–114

    CAS  PubMed Central  PubMed  Google Scholar 

  • Morgan KL, Estevez AO, Mueller CL, Cacho-Valadez B, Miranda-Vizuete A, Szewczyk NJ, Estevez M (2010) The glutaredoxin GLRX-21 functions to prevent selenium-induced oxidative stress in Caenorhabditis elegans. Toxicol Sci 118:530–543

    CAS  PubMed  Google Scholar 

  • Morgan B, Sobotta MC, Dick TP (2011) Measuring EGSH and H2O2 with roGFP2-based redox probes. Free Radic Biol Med 51:1943–1951

    CAS  PubMed  Google Scholar 

  • Muller FL (2009) A critical evaluation of cpYFP as a probe for superoxide. Free Radic Biol Med 47:1779–1780

    CAS  PubMed  Google Scholar 

  • Niethammer P, Grabher C, Look AT, Mitchison TJ (2009) A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish. Nature 459:996–999

    CAS  PubMed Central  PubMed  Google Scholar 

  • Ohashi T, Mizutani A, Murakami A, Kojo S, Ishii T, Taketani S (2002) Rapid oxidation of dichlorodihydrofluorescin with heme and hemoproteins: formation of the fluorescein is independent of the generation of reactive oxygen species. FEBS Lett 511:21–27

    CAS  PubMed  Google Scholar 

  • Oku M, Sakai Y (2012) Assessment of physiological redox state with novel FRET protein probes. Antioxid Redox Signal 16(7):698–704

    CAS  PubMed  Google Scholar 

  • Ostergaard H, Tachibana C, Winther JR (2004) Monitoring disulfide bond formation in the eukaryotic cytosol. J Cell Biol 166:337–345

    CAS  PubMed  Google Scholar 

  • Oushiki D, Kojima H, Terai T, Arita M, Hanaoka K, Urano Y, Nagano T (2010) Development and application of a near-infrared fluorescence probe for oxidative stress based on differential reactivity of linked cyanine dyes. J Am Chem Soc 132:2795–2801

    CAS  PubMed  Google Scholar 

  • Ouyang J, Hong H, Shen C, Zhao Y, Ouyang C, Dong L, Zhu J, Guo Z, Zeng K, Chen J, Zhang C, Zhang J (2008) A novel fluorescent probe for the detection of nitric oxide in vitro and in vivo. Free Radic Biol Med 45:1426–1436

    CAS  PubMed  Google Scholar 

  • Pashkow FJ (2011) Oxidative stress and inflammation in heart disease: do antioxidants have a role in treatment and/or prevention? Int J Inflamm 2011:514623

    Google Scholar 

  • Pearce LL, Gandley RE, Han W, Wasserloos K, Stitt M, Kanai AJ, McLaughlin MK, Pitt BR, Levitan ES (2000) Role of metallothionein in nitric oxide signaling as revealed by a green fluorescent fusion protein. Proc Natl Acad Sci USA 97:477–482

    CAS  PubMed  Google Scholar 

  • Poburko D, Santo-Domingo J, Demaurex N (2011) Dynamic regulation of the mitochondrial proton gradient during cytosolic calcium elevations. J Biol Chem 286:11672–11684

    CAS  PubMed  Google Scholar 

  • Rhee SG, Chang TS, Jeong W, Kang D (2010) Methods for detection and measurement of hydrogen peroxide inside and outside of cells. Mol Cells 29:539–549

    CAS  PubMed  Google Scholar 

  • Rice GC, Bump EA, Shrieve DC, Lee W, Kovacs M (1986) Quantitative analysis of cellular glutathione by flow cytometry utilizing monochlorobimane: some applications to radiation and drug resistance in vitro and in vivo. Cancer Res 46:6105–6110

    CAS  PubMed  Google Scholar 

  • Robinson KM, Janes MS, Pehar M, Monette JS, Ross MF, Hagen TM, Murphy MP, Beckman JS (2006) Selective fluorescent imaging of superoxide in vivo using ethidium-based probes. Proc Natl Acad Sci USA 103:15038–15043

    CAS  PubMed  Google Scholar 

  • Robinson KM, Janes MS, Beckman JS (2008) The selective detection of mitochondrial superoxide by live cell imaging. Nat Protoc 3:941–947

    CAS  PubMed  Google Scholar 

  • Roma LP, Duprez J, Takahashi HK, Gilon P, Wiederkehr A, Jonas JC (2012) Dynamic measurements of mitochondrial hydrogen peroxide concentration and glutathione redox state in rat pancreatic beta-cells using ratiometric fluorescent proteins: confounding effects of pH with HyPer but not roGFP1. Biochem J 441(Part 3):971–978

    CAS  PubMed  Google Scholar 

  • Rosenwasser S, Rot I, Sollner E, Meyer AJ, Smith Y, Leviatan N, Fluhr R, Friedman H (2011) Organelles contribute differentially to reactive oxygen species-related events during extended darkness. Plant Physiol 156:185–201

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sasaki E, Kojima H, Nishimatsu H, Urano Y, Kikuchi K, Hirata Y, Nagano T (2005) Highly sensitive near-infrared fluorescent probes for nitric oxide and their application to isolated organs. J Am Chem Soc 127:3684–3685

    CAS  PubMed  Google Scholar 

  • Schulz TJ, Zarse K, Voigt A, Urban N, Birringer M, Ristow M (2007) Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metab 6:280–293

    CAS  PubMed  Google Scholar 

  • Schwarzlander M, Fricker MD, Sweetlove LJ (2009) Monitoring the in vivo redox state of plant mitochondria: effect of respiratory inhibitors, abiotic stress and assessment of recovery from oxidative challenge. Biochim Biophys Acta 1787:468–475

    PubMed  Google Scholar 

  • Schwarzlander M, Logan DC, Fricker MD, Sweetlove LJ (2011) The circularly permuted yellow fluorescent protein cpYFP that has been used as a superoxide probe is highly responsive to pH but not superoxide in mitochondria: implications for the existence of superoxide ‘flashes’. Biochem J 437:381–387

    PubMed  Google Scholar 

  • Setsukinai K, Urano Y, Kakinuma K, Majima HJ, Nagano T (2003) Development of novel fluorescence probes that can reliably detect reactive oxygen species and distinguish specific species. J Biol Chem 278:3170–3175

    CAS  PubMed  Google Scholar 

  • Shepherd J, Hilderbrand SA, Waterman P, Heinecke JW, Weissleder R, Libby P (2007) A fluorescent probe for the detection of myeloperoxidase activity in atherosclerosis-associated macrophages. Chem Biol 14:1221–1231

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shulaev V, Oliver DJ (2006) Metabolic and proteomic markers for oxidative stress. New tools for reactive oxygen species research. Plant Physiol 141:367–372

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sikora A, Zielonka J, Lopez M, Joseph J, Kalyanaraman B (2009) Direct oxidation of boronates by peroxynitrite: mechanism and implications in fluorescence imaging of peroxynitrite. Free Radic Biol Med 47:1401–1407

    CAS  PubMed Central  PubMed  Google Scholar 

  • Simen Zhao B, Liang Y, Song Y, Zheng C, Hao Z, Chen PR (2010) A highly selective fluorescent probe for visualization of organic hydroperoxides in living cells. J Am Chem Soc 132(48):17065–17067

    Google Scholar 

  • Srikun D, Miller EW, Domaille DW, Chang CJ (2008) An ICT-based approach to ratiometric fluorescence imaging of hydrogen peroxide produced in living cells. J Am Chem Soc 130:4596–4597

    CAS  PubMed  Google Scholar 

  • Srikun D, Albers AE, Nam CI, Iavarone AT, Chang CJ (2010) Organelle-targetable fluorescent probes for imaging hydrogen peroxide in living cells via SNAP-Tag protein labeling. J Am Chem Soc 132:4455–4465

    CAS  PubMed Central  PubMed  Google Scholar 

  • Sun X, Shih AY, Johannssen HC, Erb H, Li P, Murphy TH (2006) Two-photon imaging of glutathione levels in intact brain indicates enhanced redox buffering in developing neurons and cells at the cerebrospinal fluid and blood–brain interface. J Biol Chem 281:17420–17431

    CAS  PubMed  Google Scholar 

  • Sun ZN, Wang HL, Liu FQ, Chen Y, Tam PK, Yang D (2009) BODIPY-based fluorescent probe for peroxynitrite detection and imaging in living cells. Org Lett 11:1887–1890

    CAS  PubMed  Google Scholar 

  • Ueno T, Urano Y, Kojima H, Nagano T (2006) Mechanism-based molecular design of highly selective fluorescence probes for nitrative stress. J Am Chem Soc 128:10640–10641

    CAS  PubMed  Google Scholar 

  • van de Bittner GC, Dubikovskaya EA, Bertozzi CR, Chang CJ (2010) In vivo imaging of hydrogen peroxide production in a murine tumor model with a chemoselective bioluminescent reporter. Proc Natl Acad Sci USA 107:21316–21321

    PubMed  Google Scholar 

  • van der Ven AJ, Mier P, Peters WH, Dolstra H, van Erp PE, Koopmans PP, van der Meer JW (1994) Monochlorobimane does not selectively label glutathione in peripheral blood mononuclear cells. Anal Biochem 217:41–47

    PubMed  Google Scholar 

  • van Lith M, Tiwari S, Pediani J, Milligan G, Bulleid NJ (2011) Real-time monitoring of redox changes in the mammalian endoplasmic reticulum. J Cell Sci 124:2349–2356

    PubMed  Google Scholar 

  • Veal EA, Day AM, Morgan BA (2007) Hydrogen peroxide sensing and signaling. Mol Cell 26: 1–14

    CAS  PubMed  Google Scholar 

  • Vikram DS, Rivera BK, Kuppusamy P (2010) In vivo imaging of free radicals and oxygen. Methods Mol Biol 610:3–27

    CAS  PubMed  Google Scholar 

  • Wang W, Fang H, Groom L, Cheng A, Zhang W, Liu J, Wang X, Li K, Han P, Zheng M, Yin J, Mattson MP, Kao JP, Lakatta EG, Sheu SS, Ouyang K, Chen J, Dirksen RT, Cheng H (2008) Superoxide flashes in single mitochondria. Cell 134:279–290

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wardman P (2007) Fluorescent and luminescent probes for measurement of oxidative and nitrosative species in cells and tissues: progress, pitfalls, and prospects. Free Radic Biol Med 43:995–1022

    CAS  PubMed  Google Scholar 

  • Waypa GB, Guzy R, Mungai PT, Mack MM, Marks JD, Roe MW, Schumacker PT (2006) Increases in mitochondrial reactive oxygen species trigger hypoxia-induced calcium responses in pulmonary artery smooth muscle cells. Circ Res 99:970–978

    CAS  PubMed  Google Scholar 

  • Weissleder R, Ntziachristos V (2003) Shedding light onto live molecular targets. Nat Med 9: 123–128

    CAS  PubMed  Google Scholar 

  • Wink DA, Hines HB, Cheng RY, Switzer CH, Flores-Santana W, Vitek MP, Ridnour LA, Colton CA (2011) Nitric oxide and redox mechanisms in the immune response. J Leukoc Biol 89: 873–891

    CAS  PubMed  Google Scholar 

  • Winterbourn CC, Hampton MB (2008) Thiol chemistry and specificity in redox signaling. Free Radic Biol Med 45:549–561

    CAS  PubMed  Google Scholar 

  • Wrona M, Patel K, Wardman P (2005) Reactivity of 2′,7′-dichlorodihydrofluorescein and dihydrorhodamine 123 and their oxidized forms toward carbonate, nitrogen dioxide, and hydroxyl radicals. Free Radic Biol Med 38:262–270

    CAS  PubMed  Google Scholar 

  • Xu X, von Lohneysen K, Soldau K, Noack D, Vu A, Friedman JS (2011) A novel approach for in vivo measurement of mouse red cell redox status. Blood 118:3694–3697

    CAS  PubMed  Google Scholar 

  • Yang D, Wang HL, Sun ZN, Chung NW, Shen JG (2006) A highly selective fluorescent probe for the detection and imaging of peroxynitrite in living cells. J Am Chem Soc 128:6004–6005

    CAS  PubMed  Google Scholar 

  • Yano T, Oku M, Akeyama N, Itoyama A, Yurimoto H, Kuge S, Fujiki Y, Sakai Y (2010) A novel fluorescent sensor protein for visualization of redox states in the cytoplasm and in peroxisomes. Mol Cell Biol 30:3758–3766

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yoo SK, Starnes TW, Deng Q, Huttenlocher A (2011) Lyn is a redox sensor that mediates leukocyte wound attraction in vivo. Nature 480:109–112

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yoshimura T, Yokoyama H, Fujii S, Takayama F, Oikawa K, Kamada H (1996) In vivo EPR detection and imaging of endogenous nitric oxide in lipopolysaccharide-treated mice. Nat Biotechnol 14:992–994

    CAS  PubMed  Google Scholar 

  • Yu F, Li P, Li G, Zhao G, Chu T, Han K (2011) A near-IR reversible fluorescent probe modulated by selenium for monitoring peroxynitrite and imaging in living cells. J Am Chem Soc 133: 11030–11033

    CAS  PubMed  Google Scholar 

  • Zhang Q, Wang SY, Nottke AC, Rocheleau JV, Piston DW, Goodman RH (2006) Redox sensor CtBP mediates hypoxia-induced tumor cell migration. Proc Natl Acad Sci USA 103: 9029–9033

    CAS  PubMed  Google Scholar 

  • Zhao Y, Jin J, Hu Q, Zhou HM, Yi J, Yu Z, Xu L, Wang X, Yang Y, Loscalzo J (2011) Genetically encoded fluorescent sensors for intracellular NADH detection. Cell Metab 14:555–566

    CAS  PubMed Central  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Redox Regulation, German Cancer Research Center (DKFZ), DKFZ-ZMBH Alliance, Im Neuenheimer Feld 280, 69120, Heidelberg, Germany

    Yuuta Fujikawa, Bruce Morgan & Tobias P. Dick

Authors
  1. Yuuta Fujikawa
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Bruce Morgan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tobias P. Dick
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Tobias P. Dick .

Editor information

Editors and Affiliations

  1. Mol.,Cel. and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA

    Ursula Jakob

  2. The Alexander Silberman Institute of Life Science, Department of Biological Chemistry, The Hebrew University of Jerusalem, Jerusalem, Israel

    Dana Reichmann

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Fujikawa, Y., Morgan, B., Dick, T.P. (2013). Fluorescent Imaging of Redox Species in Multicellular Organisms. In: Jakob, U., Reichmann, D. (eds) Oxidative Stress and Redox Regulation. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5787-5_5

Download citation

Publish with us

Policies and ethics

Search

Navigation