Hydrogen peroxide as a central redox signaling molecule in physiological oxidative stress: Oxidative eustress

Helmut Sies, Helmut Sies

Abstract

Hydrogen peroxide emerged as major redox metabolite operative in redox sensing, signaling and redox regulation. Generation, transport and capture of H2O2 in biological settings as well as their biological consequences can now be addressed. The present overview focuses on recent progress on metabolic sources and sinks of H2O2 and on the role of H2O2 in redox signaling under physiological conditions (1-10nM), denoted as oxidative eustress. Higher concentrations lead to adaptive stress responses via master switches such as Nrf2/Keap1 or NF-κB. Supraphysiological concentrations of H2O2 (>100nM) lead to damage of biomolecules, denoted as oxidative distress. Three questions are addressed: How can H2O2 be assayed in the biological setting? What are the metabolic sources and sinks of H2O2? What is the role of H2O2 in redox signaling and oxidative stress?

Keywords: H(2)O(2); Mitochondria; NADPH oxidases; Oxidative stress; Peroxiporins; Redox regulation.

Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Figures

Graphical abstract
Graphical abstract
Fig. 1
Fig. 1
Timeline of hydrogen peroxide in chemistry and biology.
Fig. 2
Fig. 2
Quantification of H2O2 production in intact perfused rat liver during decanoate oxidation. Catalase Compound I is monitored at 660–640 nm continuously against time by organ spectrophotometry. Calibration of the decanoate response is performed against the urate response. With the 1:1 stoichiometry of urate:H2O2 and measurement of the rate of urate removal in the effluent perfusate, the decanoate response is quantified to indicate an extra H2O2 production of 80 nmol H2O2/min per gram liver wet weight in this experiment. For details, see , .
Fig. 3
Fig. 3
Role of hydrogen peroxide in oxidative stress. Top: Endogenous H2O2 sources include NADPH oxidases and other oxidases (membrane-bound or free) as well as the mitochondria. The superoxide anion radical is converted to hydrogen peroxide by the three superoxide dismutases (SODs 1,2,3). Hydrogen peroxide diffusion across membranes occurs by some aquaporins (AQP), known as peroxiporins. Bottom: In green, redox signaling comprises oxidative eustress (physiological oxidative stress). In red, excessive oxidative stress leads to oxidative damage of biomolecules and disrupted redox signaling, oxidative distress. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)
Fig. 4
Fig. 4
Estimated ranges of hydrogen peroxide concentration in oxidative stress with regard to cellular responses. The intracellular physiological range likely spans between 1 and 10 up to approx. 100 nM H2O2; the arrow indicates data from normally metabolizing liver. Stress and adaptive stress responses occur at higher concentrations. Even higher exposure leads to inflammatory response, growth arrest and cell death by various mechanisms. Green and red coloring denotes predominantly beneficial or deleterious responses, respectively. An estimated 100-fold concentration gradient from extracellular to intracellular is given for rough orientation; this gradient will vary with cell type, location inside cells and the activity of enzymatic sinks (see text). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

References

    1. Marinho H.S., Real C., Cyrne L., Soares H., Antunes F. Hydrogen peroxide sensing, signaling and regulation of transcription factors. Redox. Biol. 2014;2:535–562.
    1. Cordeiro J.V., Jacinto A. The role of transcription-independent damage signals in the initiation of epithelial wound healing. Nat. Rev. Mol. Cell Biol. 2013;14:249–262.
    1. van der Vliet A., Janssen-Heininger Y.M. Hydrogen peroxide as a damage signal in tissue injury and inflammation: murderer, mediator, or messenger? J. Cell Biochem. 2014;115:427–435.
    1. Sies H. Role of metabolic H2O2 generation: redox signaling and oxidative stress. J. Biol. Chem. 2014;289:8735–8741.
    1. Stone J.R., Yang S. Hydrogen peroxide: a signaling messenger. Antioxid. Redox Signal. 2006;8:243–270.
    1. Jones D.P., Sies H. The Redox Code. Antioxid. Redox Signal. 2015;23:734–746.
    1. Sies H., Chance B. The steady state level of catalase compound I in isolated hemoglobin-free perfused rat liver. FEBS Lett. 1970;11:172–176.
    1. Sies H., Berndt C., Jones D.P. Oxidative stress. Annu. Rev. Biochem. 2017;86 (xxx-xxx)
    1. Sarsour E.H., Kalen A.L., Goswami P.C. Manganese superoxide dismutase regulates a redox cycle within the cell cycle. Antioxid. Redox. Signal. 2014;20:1618–1627.
    1. Niki E. Oxidative stress and antioxidants: distress or eustress? Arch. Biochem. Biophys. 2016;595:19–24.
    1. Aschbacher K., O'Donovan A., Wolkowitz O.M., Dhabhar F.S., Su Y., Epel E. Good stress, bad stress and oxidative stress: insights from anticipatory cortisol reactivity. Psychoneuroendocrinology. 2013;38:1698–1708.
    1. Li G., He H. Hormesis, allostatic buffering capacity and physiological mechanism of physical activity: a new theoretic framework. Med. Hypotheses. 2009;72:527–532.
    1. Lushchak V.I. Free radicals, reactive oxygen species, oxidative stress and its classification. Chem Biol. Interact. 2014;224C:164–175.
    1. Ursini F., Maiorino M., Forman H.J. Redox homeostasis: the golden mean of healthy living. Redox. Biol. 2016;8:205–215.
    1. Lazarus R.S. McGraw-Hill; New York: 1966. Psychological stress and the coping process.
    1. Selye H. Lippincott; Philadelphia: 1974. Stress without distress.
    1. Brill A.S., Williams R.J. Primary compounds of catalase and peroxidase. Biochem. J. 1961;78:253–262.
    1. Chance B., Schonbaum G.R. The nature of the primary complex of catalase. J. Biol. Chem. 1962;237:2391–2395.
    1. Oshino N., Chance B., Sies H., Bücher T. The role of H2O2 generation in perfused rat liver and the reaction of catalase compound I and hydrogen donors. Arch. Biochem. Biophys. 1973;154:117–131.
    1. Jones D.P., Thor H., Andersson B., Orrenius S. Detoxification reactions in isolated hepatocytes. Role of glutathione peroxidase, catalase, and formaldehyde dehydrogenase in reactions relating to N-demethylation by the cytochrome P-450 system. J. Biol. Chem. 1978;253:6031–6037.
    1. Chance B., Sies H., Boveris A. Hydroperoxide metabolism in mammalian organs. Physiol Rev. 1979;59:527–605.
    1. Foerster E.C., Fährenkemper T., Rabe U., Graf P., Sies H. Peroxisomal fatty acid oxidation as detected by H2O2 production in intact perfused rat liver. Biochem. J. 1981;196:705–712.
    1. Sies H. Measurement of hydrogen peroxide formation in situ. Methods Enzymol. 1981;77:15–20.
    1. Jones D.P. Intracellular catalase function: analysis of the catalatic activity by product formation in isolated liver cells. Arch. Biochem. Biophys. 1982;214:806–814.
    1. Belousov V.V., Fradkov A.F., Lukyanov K.A., Staroverov D.B., Shakhbazov K.S. Genetically encoded fluorescent indicator for intracellular hydrogen peroxide. Nat. Methods. 2006;3:281–286.
    1. Ermakova Y.G., Bilan D.S., Matlashov M.E., Mishina N.M., Markvicheva K.N. Red fluorescent genetically encoded indicator for intracellular hydrogen peroxide. Nat. Commun. 2014;5:5222.
    1. Malinouski M., Zhou Y., Belousov V.V., Hatfield D.L., Gladyshev V.N. Hydrogen peroxide probes directed to different cellular compartments. PLoS. One. 2011;6:e14564.
    1. Poburko D., Santo-Domingo J., Demaurex N. Dynamic regulation of the mitochondrial proton gradient during cytosolic calcium elevations. J. Biol. Chem. 2011;286:11672–11684.
    1. Matlashov M.E., Bogdanova Y.A., Ermakova G.V., Mishina N.M., Ermakova Y.G. Fluorescent ratiometric pH indicator SypHer2: applications in neuroscience and regenerative biology. Biochim. Biophys. Acta. 2015;1850:2318–2328.
    1. Albrecht S.C., Barata A.G., Grosshans J., Teleman A.A., Dick T.P. In vivo mapping of hydrogen peroxide and oxidized glutathione reveals chemical and regional specificity of redox homeostasis. Cell Metab. 2011;14:819–829.
    1. Gutscher M., Sobotta M.C., Wabnitz G.H., Ballikaya S., Meyer A.J. Proximity-based protein thiol oxidation by H2O2-scavenging peroxidases. J. Biol. Chem. 2009;284:31532–31540.
    1. Morgan B., Van L.K., Owusu T.N., Ezerina D., Pastor-Flores D. Real-time monitoring of basal H2O2 levels with peroxiredoxin-based probes. Nat. Chem. Biol. 2016;12:437–443.
    1. Brewer T.F., Garcia F.J., Onak C.S., Carroll K.S., Chang C.J. Chemical approaches to discovery and study of sources and targets of hydrogen peroxide redox signaling through NADPH oxidase proteins. Annu. Rev. Biochem. 2015;84:765–790.
    1. Logan A., Cocheme H.M., Li Pun P.B., Apostolova N., Smith R.A. Using exomarkers to assess mitochondrial reactive species in vivo. Biochim. Biophys. Acta. 2014;1840:923–930.
    1. Winterbourn C.C. The challenges of using fluorescent probes to detect and quantify specific reactive oxygen species in living cells. Biochim. Biophys. Acta. 2014;1840:730–738.
    1. Bedard K., Krause K.H. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev. 2007;87:245–313.
    1. Lassègue B., San M.A., Griendling K.K. Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system. Circ. Res. 2012;110:1364–1390.
    1. Brand M.D. Mitochondrial generation of superoxide and hydrogen peroxide as the source of mitochondrial redox signaling. Free Radic. Biol. Med. 2016;100:14–31.
    1. Mailloux R.J. Teaching the fundamentals of electron transfer reactions in mitochondria and the production and detection of reactive oxygen species. Redox. Biol. 2015;4:381–398.
    1. Murphy M.P. How mitochondria produce reactive oxygen species. Biochem. J. 2009;417:1–13.
    1. Go Y.M., Chandler J.D., Jones D.P. The cysteine proteome. Free Radic. Biol. Med. 2015;84:227–245.
    1. Winterbourn C.C. The biological chemistry of hydrogen peroxide. Methods Enzymol. 2013;528:3–25.
    1. Antunes F., Han D., Cadenas E. Relative contributions of heart mitochondria glutathione peroxidase and catalase to H2O2 detoxification in in vivo conditions. Free Radic. Biol. Med. 2002;33:1260–1267.
    1. Jones D.P., Eklöw L., Thor H., Orrenius S. Metabolism of hydrogen peroxide in isolated hepatocytes: relative contributions of catalase and glutathione peroxidase in decomposition of endogenously generated H2O2. Arch. Biochem. Biophys. 1981;210:505–516.
    1. Sies H., Gerstenecker C., Menzel H., Flohé L. Oxidation in the NADP system and release of GSSG from hemoglobin-free perfused rat liver during peroxidatic oxidation of glutathione by hydroperoxides. FEBS Lett. 1972;27:171–175.
    1. Sies H., Summer K.H. Hydroperoxide-metabolizing systems in rat liver. Eur. J. Biochem. 1975;57:503–512.
    1. Wagner B.A., Witmer J.R., van 't Erve T.J., Buettner G.R. An assay for the rate of removal of extracellular hydrogen peroxide by cells. Redox. Biol. 2013;1:210–217.
    1. Henzler T., Steudle E. Transport and metabolic degradation of hydrogen peroxide in Chara corallina: model calculations and measurements with the pressure probe suggest transport of H2O2 across water channels. J. Exp. Bot. 2000;51:2053–2066.
    1. Bienert G.P., Schjoerring J.K., Jahn T.P. Membrane transport of hydrogen peroxide. Biochim. Biophys. Acta. 2006;1758:994–1003.
    1. Bienert G.P., Moller A.L., Kristiansen K.A., Schulz A., Moller I.M. Specific aquaporins facilitate the diffusion of hydrogen peroxide across membranes. J. Biol. Chem. 2007;282:1183–1192.
    1. Antunes F., Cadenas E. Estimation of H2O2 gradients across biomembranes. FEBS Lett. 2000;475:121–126.
    1. Huang B.K., Sikes H.D. Quantifying intracellular hydrogen peroxide perturbations in terms of concentration. Redox. Biol. 2014;2:955–962.
    1. Marinho H.S., Cyrne L., Cadenas E., Antunes F. The cellular steady-state of H2O2: latency concepts and gradients. Methods Enzymol. 2013;527:3–19.
    1. Forman H.J., Bernardo A., Davies K.J. What is the concentration of hydrogen peroxide in blood and plasma? Arch. Biochem. Biophys. 2016;603:48–53.
    1. Bleier L., Wittig I., Heide H., Steger M., Brandt U., Dröse S. Generator-specific targets of mitochondrial reactive oxygen species. Free Radic. Biol. Med. 2015;78:1–10.
    1. Booth D.M., Enyedi B., Geiszt M., Varnai P., Hajnoczky G. Redox nanodomains are induced by and control calcium signaling at the ER-mitochondrial interface. Mol. Cell. 2016;63:240–248.
    1. Edgar R.S., Green E.W., Zhao Y., van O.G., Olmedo M. Peroxiredoxins are conserved markers of circadian rhythms. Nature. 2012;485:459–464.
    1. Kil I.S., Lee S.K., Ryu K.W., Woo H.A., Hu M.C. Feedback control of adrenal steroidogenesis via H2O2-dependent, reversible inactivation of peroxiredoxin III in mitochondria. Mol. Cell. 2012;46:584–594.
    1. Putker M., O'Neill J.S. Reciprocal control of the circadian clock and cellular redox state - a critical appraisal. Mol. Cells. 2016;39:6–19.
    1. Cebula M., Schmidt E.E., Arnér E.S. TrxR1 as a potent regulator of the Nrf2-Keap1 response system. Antioxid. Redox Signal. 2015;23:823–853.
    1. Espinosa-Diez C., Miguel V., Mennerich D., Kietzmann T., Sanchez-Perez P. Antioxidant responses and cellular adjustments to oxidative stress. Redox Biol. 2015;6:183–197.
    1. Hansen J.M., Moriarty-Craige S., Jones D.P. Nuclear and cytoplasmic peroxiredoxin-1 differentially regulate NF-kappaB activities. Free Radic. Biol. Med. 2007;43:282–288.
    1. Lee J., Giordano S., Zhang J. Autophagy, mitochondria and oxidative stress: cross-talk and redox signalling. Biochem. J. 2012;441:523–540.
    1. Scherz-Shouval R., Elazar Z. Regulation of autophagy by ROS: physiology and pathology. Trends Biochem. Sci. 2011;36:30–38.
    1. Frank M., Duvezin-Caubet S., Koob S., Occhipinti A., Jagasia R. Mitophagy is triggered by mild oxidative stress in a mitochondrial fission dependent manner. Biochim. Biophys. Acta. 2012;1823:2297–2310.
    1. Zhang L., Wang K., Lei Y., Li Q., Nice E.C., Huang C. Redox signaling: potential arbitrator of autophagy and apoptosis in therapeutic response. Free Radic. Biol. Med. 2015;89:452–465.
    1. Alvarez L.A., Kovacic L., Rodriguez J., Gosemann J.H., Kubica M. NADPH oxidase-derived H2O2 subverts pathogen signaling by oxidative phosphotyrosine conversion to PB-DOPA. Proc. Natl. Acad. Sci. U. S. A. 2016;113:10406–10411.
    1. Altintas A., Davidsen K., Garde C., Mortensen U.H., Brasen J.C. High-resolution kinetics and modeling of hydrogen peroxide degradation in live cells. Free Radic. Biol. Med. 2016;101:143–153.
    1. Brito P.M., Antunes F. Estimation of kinetic parameters related to biochemical interactions between hydrogen peroxide and signal transduction proteins. Front Chem. 2014;2:82.
    1. Lim J.B., Langford T.F., Huang B.K., Deen W.M., Sikes H.D. A reaction-diffusion model of cytosolic hydrogen peroxide. Free Radic. Biol. Med. 2016;90:85–90.
    1. Treberg J.R., Munro D., Banh S., Zacharias P., Sotiri E. Differentiating between apparent and actual rates of H2O2 metabolism by isolated rat muscle mitochondria to test a simple model of mitochondria as regulators of H2O2 concentration. Redox Biol. 2015;5:216–224.
    1. Bilan D.S., Pase L., Joosen L., Gorokhovatsky A.Y., Ermakova Y.G. HyPer-3: a genetically encoded H(2)O(2) probe with improved performance for ratiometric and fluorescence lifetime imaging. ACS Chem. Biol. 2013;8:535–542.
    1. Forman H.J., Maiorino M., Ursini F. Signaling functions of reactive oxygen species. Biochemistry. 2010;49:835–842.
    1. Imlay J.A. Transcription factors that defend bacteria against reactive oxygen species. Annu. Rev. Microbiol. 2015;69:93–108.
    1. Flohé L. The impact of thiol peroxidases on redox regulation. Free Radic. Res. 2016;50:126–142.
    1. Garcia-Santamarina S., Boronat S., Hidalgo E. Reversible cysteine oxidation in hydrogen peroxide sensing and signal transduction. Biochemistry. 2014;53:2560–2580.
    1. Poole L.B., Karplus P.A., Claiborne A. Protein sulfenic acids in redox signaling. Annu. Rev. Pharmacol. Toxicol. 2004;44:325–347.
    1. Poole L.B. The basics of thiols and cysteines in redox biology and chemistry. Free Radic. Biol. Med. 2015;80:148–157.
    1. Cho S.H., Lee C.H., Ahn Y., Kim H., Kim H. Redox regulation of PTEN and protein tyrosine phosphatases in H2O2 mediated cell signaling. FEBS Lett. 2004;560:7–13.
    1. Santos C.X., Hafstad A.D., Beretta M., Zhang M., Molenaar C. Targeted redox inhibition of protein phosphatase 1 by Nox4 regulates eIF2alpha-mediated stress signaling. EMBO J. 2016;35:319–334.
    1. Petrat F., de Groot H.,, Sustmann R., Rauen U. The chelatable iron pool in living cells: a methodically defined quantity. Biol. Chem. 2002;383:489–502.
    1. Mantzaris M.D., Bellou S., Skiada V., Kitsati N., Fotsis T., Galaris D. Intracellular labile iron determines H2O2-induced apoptotic signaling via sustained activation of ASK1/JNK-p38 axis. Free Radic. Biol. Med. 2016;97:454–465.
    1. Nauseef W.M. Detection of superoxide anion and hydrogen peroxide production by cellular NADPH oxidases. Biochim. Biophys. Acta. 2014;1840:757–767.
    1. Reczek C.R., Chandel N.S. ROS-dependent signal transduction. Curr. Opin. Cell Biol. 2015;33:8–13.
    1. Riemer J., Schwarzländer M., Conrad M., Herrmann J.M. Thiol switches in mitochondria: operation and physiological relevance. Biol. Chem. 2015;396:465–482.
    1. Go Y.M., Jones D.P. The redox proteome. J. Biol. Chem. 2013;288:26512–26520.
    1. Yang J., Carroll K.S., Liebler D.C. The expanding landscape of the thiol redox proteome. Mol. Cell Proteom. 2016;15:1–11.
    1. Rhee S.G., Woo H.A. Multiple functions of peroxiredoxins: peroxidases, sensors and regulators of the intracellular messenger H2O2, and protein chaperones. Antioxid. Redox Signal. 2011;15:781–794.
    1. Sobotta M.C., Liou W., Stocker S., Talwar D., Oehler M. Peroxiredoxin-2 and STAT3 form a redox relay for H2O2 signaling. Nat. Chem. Biol. 2015;11:64–70.
    1. Holmström K.M., Finkel T. Cellular mechanisms and physiological consequencesof redox-dependent signalling. Nat. Rev. Mol. Cell Biol. 2014;15:411–421.
    1. Sanchez-Gomez F.J., Calvo E., Breton-Romero R., Fierro-Fernandez M., Anilkumar N. NOX4-dependent hydrogen peroxide promotes shear stress-induced SHP2 sulfenylation and eNOS activation. Free Radic. Biol. Med. 2015;89:419–430.
    1. Schröder K., Zhang M., Benkhoff S., Mieth A., Pliquett R. Nox4 is a protective reactive oxygen species generating vascular NADPH oxidase. Circ. Res. 2012;110:1217–1225.
    1. Byon C.H., Heath J.M., Chen Y. Redox signaling in cardiovascular pathophysiology: a focus on hydrogen peroxide and vascular smooth muscle cells. Redox Biol. 2016;9:244–253.
    1. Niethammer P., Grabher C., Look A.T., Mitchison T.J. A tissue-scale gradient of hydrogen peroxide mediates rapid wound detection in zebrafish. Nature. 2009;459:996–999.
    1. Love N.R., Chen Y., Ishibashi S., Kritsiligkou P., Lea R. Amputation-induced reactive oxygen species are required for successful Xenopus tadpole tail regeneration. Nat. Cell Biol. 2013;15:222–228.
    1. Niethammer P. The early wound signals. Curr. Opin. Genet. Dev. 2016;40:17–22.
    1. Gauron C., Meda F., Dupont E., Albadri S., Quenech'Du N. Hydrogen peroxide (H2O2) controls axon pathfinding during zebrafish development. Dev. Biol. 2016;414:133–141.
    1. Medrano-Fernandez I., Bestetti S., Bertolotti M., Bienert G.P., Bottino C. Stress regulates aquaporin-8 permeability to impact cell growth and survival. Antioxid. Redox Signal. 2016;24:1031–1044.
    1. Miller E.W., Dickinson B.C., Chang C.J. Aquaporin-3 mediates hydrogen peroxide uptake to regulate downstream intracellular signaling. Proc. Natl. Acad. Sci. U.S.A. 2010;107:15681–15686.
    1. Hara-Chikuma M., Satooka H., Watanabe S., Honda T., Miyachi Y. Aquaporin-3-mediated hydrogen peroxide transport is required for NF-kappaB signalling in keratinocytes and development of psoriasis. Nat. Commun. 2015;6:7454.
    1. Appenzeller-Herzog C., Banhegyi G., Bogeski I., Davies K.J., Delaunay-Moisan A. Transit of HO across the endoplasmic reticulum membrane is not sluggish. Free Radic. Biol. Med. 2016;94:157–160.
    1. Schwarzländer M., Dick T.P., Meyer A.J., Morgan B. Dissecting redox biology using fluorescent protein sensors. Antioxid. Redox Signal. 2016;24:680–712.
    1. Bilan D.S., Belousov V.V. HyPer family probes: state of the art. Antioxid. Redox Signal. 2016;24:731–751.
    1. Rindler P.M., Cacciola A., Kinter M., Szweda L.I. Catalase-dependent H2O2 consumption by cardiac mitochondria and redox-mediated loss in insulin signaling. Am. J. Physiol. Heart Circ. Physiol. 2016;311:H1091–H1096.
    1. Böhm B., Heinzelmann S., Motz M., Bauer G. Extracellular localization of catalase is associated with the transformed state of malignant cells. Biol. Chem. 2015;396:1339–1356.
    1. Matlashov M.E., Belousov V.V., Enikolopov G. How much H2O2 is produced by recombinant D-amino acid oxidase in mammalian cells? Antioxid. Redox Signal. 2014;20:1039–1044.
    1. Mishina N.M., Markvicheva K.N., Fradkov A.F., Zagaynova E.V., Schultz C. Imaging H2O2 microdomains in receptor tyrosine kinases signaling. Methods Enzymol. 2013;526:175–187.
    1. Willems P.H., Rossignol R., Dieteren C.E., Murphy M.P., Koopman W.J. Redox homeostasis and mitochondrial dynamics. Cell Metab. 2015;22:207–218.
    1. Lopez-Fabuel I., Le D.J., Logan A., James A.M., Bonvento G. Complex I assembly into supercomplexes determines differential mitochondrial ROS production in neurons and astrocytes. Proc. Natl. Acad. Sci. U.S.A. 2016;113:13063–13068.
    1. Brand M.D., Goncalves R.L., Orr A.L., Vargas L., Gerencser A.A. Suppressors of superoxide-H2O2 production at site IQ of mitochondrial complex I protect against stem cell hyperplasia and ischemia-reperfusion injury. Cell Metab. 2016;24:582–592.
    1. Finkel T., Menazza S., Holmström K.M., Parks R.J., Liu J. The ins and outs of mitochondrial calcium. Circ. Res. 2015;116:1810–1819.
    1. Görlach A., Bertram K., Hudecova S., Krizanova O. Calcium and ROS: a mutual interplay. Redox. Biol. 2015;6:260–271.
    1. Carafoli E., Krebs J. Why calcium? How calcium became the best communicator. J. Biol. Chem. 2016;291:20849–20857.
    1. Krols M., Bultynck G., Janssens S. ER-Mitochondria contact sites: a new regulator of cellular calcium flux comes into play. J. Cell Biol. 2016;214:367–370.
    1. Raturi A., Gutierrez T., Ortiz-Sandoval C., Ruangkittisakul A., Herrera-Cruz M.S. TMX1 determines cancer cell metabolism as a thiol-based modulator of ER-mitochondria Ca2+ flux. J. Cell Biol. 2016;214:433–444.
    1. Bagulho A., Vilas-Boas F., Pena A., Peneda C., Santos F.C. The extracellular matrix modulates H2O2 degradation and redox signaling in endothelial cells. Redox Biol. 2015;6:454–460.
    1. Feine I., Pinkas I., Salomon Y., Scherz A. Local oxidative stress expansion through endothelial cells--a key role for gap junction intercellular communication. PLoS. One. 2012;7:e41633.
    1. Ghezzi P., Chan P. Redox proteomics applied to the thiol secretome. Antioxid. Redox Signal. 2016 (PMID:27139336)
    1. Nathan C., Cunningham-Bussel A. Beyond oxidative stress: an immunologist's guide to reactive oxygen species. Nat. Rev. Immunol. 2013;13:349–361.
    1. Huang B.K., Stein K.T., Sikes H.D. Modulating and measuring intracellular H2O2 using genetically encoded tools to study its toxicity to human cells. ACS Synth. Biol. 2016 (PMID:27428287)

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren