Influence of vitamin C and vitamin E on redox signaling: implications for exercise adaptations

Cobley, James N.; McHardy, Helen; Morton, James P.; Nikolaidis, Michalis G.; Close, Graeme L.

doi:10.1016/j.freeradbiomed.2015.03.018

Cited by 118Exercise and Physiological ResponsesAntioxidant Activity and Oxidative StressVitamin C and Antioxidants Research

Influence of vitamin C and vitamin E on redox signaling: implications for exercise adaptations

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Cobley, James N., McHardy, Helen, Morton, James P., Nikolaidis, Michalis G., Close, Graeme L.·2015·Free Radical Biology and Medicine

DOI 10.1016/j.freeradbiomed.2015.03.018

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Abstract

The exogenous antioxidants vitamin C (ascorbate) and vitamin E (α-tocopherol) often blunt favorable cell signaling responses to exercise, suggesting that redox signaling contributes to exercise adaptations. Current theories posit that this antioxidant paradigm interferes with redox signaling by attenuating exercise-induced reactive oxygen species (ROS) and reactive nitrogen species (RNS) generation. The well-documented in vitro antioxidant actions of ascorbate and α-tocopherol and characterization of the type and source of the ROS/RNS produced during exercise theoretically enable identification of redox-dependent mechanisms responsible for the blunting of favorable cell signaling responses to exercise. This review aimed to apply this reasoning to determine how the aforementioned antioxidants might attenuate exercise-induced ROS/RNS production. The principal outcomes of this analysis are (1) neither antioxidant is likely to attenuate nitric oxide signaling either directly (reaction with nitric oxide) or indirectly (reaction with derivatives, e.g., peroxynitrite); (2) neither antioxidant reacts appreciably with hydrogen peroxide, a key effector of redox signaling; (3) ascorbate but not α-tocopherol has the capacity to attenuate exercise-induced superoxide generation; and (4) alternate mechanisms, namely pro-oxidant side reactions and/or reduction of bioactive oxidized macromolecule adducts, are unlikely to interfere with exercise-induced redox signaling. Out of all the possibilities considered, ascorbate-mediated suppression of superoxide generation with attendant implications for hydrogen peroxide signaling is arguably the most cogent explanation for blunting of favorable cell signaling responses to exercise. However, this mechanism is dependent on ascorbate accumulating at sites rich in NADPH oxidases, principal contributors to contraction-mediated superoxide generation, and outcompeting nitric oxide and superoxide dismutase isoforms. The major conclusions of this review are: (1) direct evidence for interference of ascorbate and α-tocopherol with exercise-induced ROS/RNS production is lacking; (2) theoretical analysis reveals that both antioxidants are unlikely to have a major impact on exercise-induced redox signaling; and (3) it is worth considering alternate redox-independent mechanisms.

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There could be a case for some polyphenolic compounds, such as tart cherry juice, to be supplemented post-exercise to attenuate muscle soreness, although whether this is through a direct scavenging effect remains unclear.
“There could also be a case for some polyphenolic compounds to be supplemented post-exercise, such as tart cherry juice [163] to attenuate muscle soreness although if this is through a direct scavenging effect remains unclear (see point 2 above and reference [148] for criteria that need to fulfilled to satisfy a scavenging affect).”
From New strategies in sport nutrition to increase exercise performance (2016) · cites this paper as [148]
Exercise-induced disruptions in skeletal muscle homeostasis regulate exercise adaptations with repeated activation.
“It is now well recognized that exercise-induced disruptions in skeletal muscle homeostasis regulate exercise adaptations with repeated activation [148,149] (Figure 1)”
From New strategies in sport nutrition to increase exercise performance (2016) · cites this paper as [148]
Repeated exercise bouts (training) induce disruption in skeletal muscle homeostasis that regulate training adaptations.
“It is accepted that repeated exercise bouts (i.e. training) induce disruption in skeletal muscle homeostasis that regulate training adaptations [62,63].”
From Sleep and Nutrition Interactions: Implications for Athletes (2019) · cites this paper as [63]

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Exercise Increases Mitochondrial PGC-1α Content and Promotes Nuclear-Mitochondrial Cross-talk to Coordinate Mitochondrial Biogenesis
Safdar, A., Little, J. P., Stokl, A., Hettinga, B. P., Akhtar, M., & Tarnopolsky, M. A. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.211466 · Cited by 309 · see citing works
Retracted
Superoxide Dismutase
McCord, J. M., & Fridovich, I. (1969) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)63504-5 · Cited by 12,952 · see citing works
How mitochondria produce reactive oxygen species
Murphy, M. P. (2009) · Biochemical Journal · doi:10.1042/bj20081386 · Cited by 8,207 · see citing works
Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxide
Beckman, J. S., Beckman, T. W., Chen, J., Marshall, P. A., & Freeman, B. A. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.4.1620 · Cited by 7,029 · see citing works
Targeting of HIF-α to the von Hippel-Lindau Ubiquitylation Complex by O 2 -Regulated Prolyl Hydroxylation
Jaakkola, P., Mole, D. R., Tian, Y.-M., Wilson, M. I., Gielbert, J., Gaskell, S. J., Kriegsheim, A. V., Hebestreit, H. F., Mukherji, M., Schofield, C. J., et al. (2001) · Science · doi:10.1126/science.1059796 · Cited by 5,535 · see citing works
Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly
Beckman, J. S., & Koppenol, W. H. (1996) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1996.271.5.c1424 · Cited by 5,513 · see citing works
Vascular endothelial cells synthesize nitric oxide from L-arginine
Palmer, R. M. J., Ashton, D., & Moncada, S. (1988) · Nature · doi:10.1038/333664a0 · Cited by 4,745 · see citing works
ROS as signalling molecules: Mechanisms that generate specificity in ROS homeostasis
D'Autréaux, B., & Toledano, M. B. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2256 · Cited by 3,642 · see citing works
Reconciling the chemistry and biology of reactive oxygen species
Winterbourn, C. C. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.85 · Cited by 2,504 · see citing works
Exercise-Induced Oxidative Stress: Cellular Mechanisms and Impact on Muscle Force Production
Powers, S. K., & Jackson, M. J. (2008) · Physiological Reviews · doi:10.1152/physrev.00031.2007 · Cited by 2,459 · see citing works
The role of iron and reactive oxygen species in cell death
Dixon, S. J., & Stockwell, B. R. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1416 · Cited by 2,381 · see citing works
Signal transduction by reactive oxygen species
Finkel, T. (2011) · Journal of Cell Biology · doi:10.1083/jcb.201102095 · Cited by 2,322 · see citing works
Measuring reactive species and oxidative damage in vivo and in cell culture: how should you do it and what do the results mean?
Halliwell, B., & Whiteman, M. (2004) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0705776 · Cited by 2,238 · see citing works
H 2 O 2 , a Necessary Evil for Cell Signaling
Rhee, S. G. (2006) · Science · doi:10.1126/science.1130481 · Cited by 2,160 · see citing works
Protein S-nitrosylation: Purview and parameters
Hess, D. T., Matsumoto, A., Kim, S.-O., Marshall, H. E., & Stamler, J. S. (2005) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1569 · Cited by 2,153 · see citing works
Cellular mechanisms and physiological consequences of redox-dependent signalling
Holmström, K. M., & Finkel, T. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3801 · Cited by 2,093 · see citing works
Exercise Metabolism and the Molecular Regulation of Skeletal Muscle Adaptation
Egan, B., & Zierath, J. R. (2013) · Cell Metabolism · doi:10.1016/j.cmet.2012.12.012 · Cited by 2,084 · see citing works
Oxygen sensing by HIF hydroxylases
Schofield, C. J., & Ratcliffe, P. J. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1366 · Cited by 2,068 · see citing works
Adaptations of skeletal muscle to endurance exercise and their metabolic consequences
Holloszy, J. O., & Coyle, E. F. (1984) · Journal of Applied Physiology · doi:10.1152/jappl.1984.56.4.831 · Cited by 1,985 · see citing works
Measuring reactive oxygen and nitrogen species with fluorescent probes: challenges and limitations
Kalyanaraman, B., Darley-Usmar, V. M., Davies, K. J. A., Dennery, P. A., Forman, H. J., Grisham, M. B., Mann, G. E., Moore, K. P., Roberts, L. J., & Ischiropoulos, H. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.09.030 · Cited by 1,795 · see citing works
Redefining Oxidative Stress
Jones, D. P. (2006) · Antioxidants & Redox Signaling · doi:10.1089/ars.2006.8.1865 · Cited by 1,726 · see citing works
Nrf2:INrf2 (Keap1) signaling in oxidative stress
Kaspar, J. W., Niture, S. K., & Jaiswal, A. K. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.07.035 · Cited by 1,646 · see citing works
Antioxidants prevent health-promoting effects of physical exercise in humans
Ristow, M., Zarse, K., Oberbach, A., Klöting, N., Birringer, M., Kiehntopf, M., Stumvoll, M., Kahn, C. R., & Blüher, M. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903485106 · Cited by 1,582 · see citing works
Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals?
Giorgio, M., Trinei, M., Migliaccio, E., & Pelicci, P. G. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2240 · Cited by 1,441 · see citing works
Peroxiredoxin Evolution and the Regulation of Hydrogen Peroxide Signaling
Wood, Z. A., Poole, L. B., & Karplus, P. A. (2003) · Science · doi:10.1126/science.1080405 · Cited by 1,369 · see citing works
Cell-signalling dynamics in time and space
Kholodenko, B. N. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1838 · Cited by 1,347 · see citing works
Metallothionein: the multipurpose protein
Coyle, P. V., Philcox, J. C., Carey, L. C., & Rofe, A. M. (2002) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-002-8454-2 · Cited by 1,305 · see citing works
Thiol chemistry and specificity in redox signaling
Winterbourn, C. C., & Hampton, M. B. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.05.004 · Cited by 1,226 · see citing works
Radical-free biology of oxidative stress
Jones, D. P. (2008) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00283.2008 · Cited by 1,213 · see citing works
A Dynamic Pathway for Calcium-Independent Activation of CaMKII by Methionine Oxidation
Erickson, J. R., Joiner, M.-L. A., Guan, X., Kutschke, W., Yang, J., Oddis, C. V., Bartlett, R. K., Lowe, J. S., O'Donnell, S. E., Aykin-Burns, N., et al. (2008) · Cell · doi:10.1016/j.cell.2008.02.048 · Cited by 1,122 · see citing works
Physiology of Nitric Oxide in Skeletal Muscle
Stamler, J. S., & Meissner, G. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.1.209 · Cited by 1,080 · see citing works
Vitamins C and E: Beneficial effects from a mechanistic perspective
Traber, M. G., & Stevens, J. F. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.05.017 · Cited by 1,076 · see citing works
Pharmacologic ascorbic acid concentrations selectively kill cancer cells: Action as a pro-drug to deliver hydrogen peroxide to tissues
Chen, Q., Espey, M. G., Krishna, M. C., Mitchell, J. B., Corpe, C. P., Buettner, G. R., Shacter, E., & Levine, M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506390102 · Cited by 1,075 · see citing works
Ascorbic acid: Chemistry, biology and the treatment of cancer
Du, J., Cullen, J. J., & Buettner, G. R. (2012) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2012.06.003 · Cited by 1,071 · see citing works
Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo
Meng, T.-C., Fukada, T., & Tonks, N. K. (2002) · Molecular Cell · doi:10.1016/s1097-2765(02)00445-8 · Cited by 1,040 · see citing works
Moderate exercise is an antioxidant: Upregulation of antioxidant genes by training
Gomez-Cabrera, M.-C., Domenech, E., & Viña, J. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.02.001 · Cited by 1,020 · see citing works
Lipid peroxidation: Physiological levels and dual biological effects
Niki, E. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.05.032 · Cited by 1,006 · see citing works
Investigating Mitochondrial Redox Potential with Redox-sensitive Green Fluorescent Protein Indicators
Hanson, G. T., Aggeler, R., Oglesbee, D., Cannon, M., Capaldi, R. A., Tsien, R. Y., & Remington, S. J. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m312846200 · Cited by 988 · see citing works
Acute Exercise Remodels Promoter Methylation in Human Skeletal Muscle
Barrès, R., Yan, J., Egan, B., Treebak, J. T., Rasmussen, M., Fritz, T., Caidahl, K., Krook, A., O'Gorman, D. J., & Zierath, J. R. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.01.001 · Cited by 965 · cited 1× · see citing works
“Of interest, ascorbate can regulate the activ ity of enzymes implicated in the regulation 515 of histone methylation [194-195], an epigenetic pro cess that regulates exercise adaptations 516 [196].”
Background
Free radicals and antioxidants: updating a personal view
Halliwell, B. B. (2012) · Nutrition Reviews · doi:10.1111/j.1753-4887.2012.00476.x · Cited by 918 · see citing works
Natural forms of vitamin E: metabolism, antioxidant, and anti-inflammatory activities and their role in disease prevention and therapy
Jiang, Q. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.03.035 · Cited by 912 · see citing works
Peroxynitrite, a Stealthy Biological Oxidant
Radí, R. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.r113.472936 · Cited by 891 · see citing works
Fluorescent and luminescent probes for measurement of oxidative and nitrosative species in cells and tissues: Progress, pitfalls, and prospects
Wardman, P. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.06.026 · Cited by 863 · see citing works
Hydrogen peroxide sensing, signaling and regulation of transcription factors
Marinho, H. S., Real, C., Cyrne, L., Soares, H., & Antunes, F. (2014) · Redox Biology · doi:10.1016/j.redox.2014.02.006 · Cited by 851 · see citing works
Oral administration of vitamin C decreases muscle mitochondrial biogenesis and hampers training-induced adaptations in endurance performance
Gomez-Cabrera, M.-C., Domenech, E., Romagnoli, M., Arduini, A., Borras, C., Pallardo, F. V., Sastre, J., & Viña, J. (2008) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/87.1.142 · Cited by 844 · see citing works
Unraveling the biological roles of reactive oxygen species
Murphy, M. P., Holmgren, A., Larsson, N.-G., Halliwell, B., Chang, C. J., Kalyanaraman, B., Rhee, S. G., Thornalley, P. J., Partridge, L., Gems, D., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.03.010 · Cited by 836 · see citing works
Signaling Functions of Reactive Oxygen Species
Forman, H. J., Maiorino, M., & Ursini, F. (2010) · Biochemistry · doi:10.1021/bi9020378 · Cited by 827 · see citing works
Redox-based regulation of signal transduction: principles, pitfalls, and promises
Janssen-Heininger, Y. M. W., Mossman, B. T., Heintz, N. H., Forman, H. J., Kalyanaraman, B., Finkel, T., Stamler, J. S., Rhee, S. G., & van der Vliet, A. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.03.011 · Cited by 784 · see citing works
Chemical biology of peroxynitrite: Kinetics, diffusion, and radicals
Ferrer-Sueta, G., & Radi, R. (2009) · ACS Chemical Biology · doi:10.1021/cb800279q · Cited by 776 · see citing works
The Molecular Bases of Training Adaptation
Coffey, V. G., & Hawley, J. A. (2007) · Sports Medicine · doi:10.2165/00007256-200737090-00001 · Cited by 756 · see citing works
Unraveling peroxynitrite formation in biological systems
Radi, R., Peluffo, G., Alvarez, M. N., Naviliat, M., & Cayota, A. (2001) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00373-7 · Cited by 735 · see citing works
Role of Metabolic H2O2 Generation
Sies, H. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.r113.544635 · Cited by 734 · see citing works
Intracellular messenger function of hydrogen peroxide and its regulation by peroxiredoxins
Rhee, S. G., Kang, S. W., Jeong, W., Chang, T.-S., Yang, K., & Woo, H. A. (2005) · Current Opinion in Cell Biology · doi:10.1016/j.ceb.2005.02.004 · Cited by 709 · see citing works
How do nutritional antioxidants really work: Nucleophilic tone and para-hormesis versus free radical scavenging in vivo
Forman, H. J., Davies, K. J. A., & Ursini, F. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.05.045 · Cited by 707 · see citing works
Peroxynitrite reductase activity of bacterial peroxiredoxins
Bryk, R., Griffin, P. R., & Nathan, C. (2000) · Nature · doi:10.1038/35025109 · Cited by 679 · see citing works
Role of vitamin E as a lipid-soluble peroxyl radical scavenger: in vitro and in vivo evidence
Niki, E. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.03.022 · Cited by 677 · see citing works
Nox family NADPH oxidases: Molecular mechanisms of activation.
Brandes, R., Weissmann, N., & Schröder, K. (2014) · Free Radical Biology & Medicine · doi:10.1016/j.freeradbiomed.2014.07.046 · Cited by 660 · see citing works
Regulation of Reactive Oxygen Species Generation in Cell Signaling
Bae, Y. S., Oh, H., Rhee, S. G., & Yoo, Y. D. (2011) · Molecules and Cells · doi:10.1007/s10059-011-0276-3 · Cited by 660 · see citing works
The antioxidant paradox
Halliwell, B. (2000) · The Lancet · doi:10.1016/s0140-6736(00)02075-4 · Cited by 655 · see citing works
Redox compartmentalization in eukaryotic cells.
Go, Y., & Jones, D. P. (2008) · Biochimica et Biophysica Acta · doi:10.1016/j.bbagen.2008.01.011 · Cited by 635 · see citing works
Reversible oxidation and inactivation of the tumor suppressor PTEN in cells stimulated with peptide growth factors
Kwon, J., Lee, S.-R., Yang, K.-S., Ahn, Y., Kim, Y. J., Stadtman, E. R., & Rhee, S. G. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407396101 · Cited by 631 · see citing works
Signalling ballet in space and time
Kholodenko, B. Ν., Hancock, J. F., & Kölch, W. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2901 · Cited by 618 · see citing works
Oxygen Consumption and Usage During Physical Exercise: The Balance Between Oxidative Stress and ROS-Dependent Adaptive Signaling
Radak, Z. O., Zhao, Z., Koltai, E., Ohno, H., & Atalay, M. (2012) · Antioxidants and Redox Signaling · doi:10.1089/ars.2011.4498 · Cited by 616 · see citing works
Inactivation of Peroxiredoxin I by Phosphorylation Allows Localized H2O2 Accumulation for Cell Signaling
Woo, H. A., Yim, S. H., Shin, D. H., Kang, D., Yu, D., & Rhee, S. G. (2010) · Cell · doi:10.1016/j.cell.2010.01.009 · Cited by 613 · see citing works
Peroxiredoxin-2 and STAT3 form a redox relay for H2O2 signaling
Sobotta, M. C., Liou, W., Stöcker, S., Talwar, D., Oehler, M., Ruppert, T., Scharf, A. N. D., & Dick, T. P. (2014) · Nature Chemical Biology · doi:10.1038/nchembio.1695 · Cited by 598 · see citing works
Peroxynitrite reaction with carbon dioxide/bicarbonate. Kinetics and influence on peroxynitrite-mediated oxidations
Denicola, A., Freeman, B. A., Trujillo, M., & Radi, R. (1996) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1996.0363 · Cited by 593 · see citing works
Basic Principles and Emerging Concepts in the Redox Control of Transcription Factors
Brigelius‐Flohé, R., & Flohé, L. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3534 · Cited by 576 · see citing works
Endothelial aging
BRANDES, R., FLEMING, I., & BUSSE, R. (2005) · Cardiovascular Research · doi:10.1016/j.cardiores.2004.12.027 · Cited by 563 · see citing works
Repeated transient mRNA bursts precede increases in transcriptional and mitochondrial proteins during training in human skeletal muscle: Molecular responses during mitochondrial biogenesis
Perry, C. G. R., Lally, J., Holloway, G. P., Heigenhauser, G. J. F., Bonen, A., & Spriet, L. L. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.199448 · Cited by 559 · see citing works
Nitrogen dioxide and carbonate radical anion: two emerging radicals in biology
Augusto, O., Bonini, M. G., Amanso, A. M., Linares, E., Santos, C. C. X., & De Menezes, S. L. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(02)00786-4 · Cited by 555 · see citing works
Oxidative stress in cell culture: an under‐appreciated problem?
Halliwell, B. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00235-7 · Cited by 534 · see citing works
Protein denitrosylation: enzymatic mechanisms and cellular functions
Benhar, M., Forrester, M. T., & Stamler, J. S. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2764 · Cited by 519 · see citing works
Update on Mechanism and Catalytic Regulation in the NO Synthases
Stuehr, D. J., Santolini, J., Wang, Z., Wei, C., & Adak, S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.r400017200 · Cited by 516 · see citing works
Rapid reaction between peroxonitrite ion and carbon dioxide: Implications for biological activity
Lymar, S. V., & Hurst, J. K. (1995) · Journal of the American Chemical Society · doi:10.1021/ja00139a027 · Cited by 515 · see citing works
Sending Signals Dynamically
Smock, R. G., & Gierasch, L. M. (2009) · Science · doi:10.1126/science.1169377 · Cited by 508 · see citing works
Decreasing xanthine oxidase‐mediated oxidative stress prevents useful cellular adaptations to exercise in rats
Gómez‐Cabrera, M. C., Borrás, C., Pallardó, F. V., Sastre, J., Ji, L. L., & Viña, J. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2004.080564 · Cited by 477 · see citing works
Mechanisms of reversible protein glutathionylation in redox signaling and oxidative stress
Gallogly, M. M., & Mieyal, J. J. (2007) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2007.06.003 · Cited by 470 · see citing works
The Biological Chemistry of Hydrogen Peroxide
Winterbourn, C. C. (2013) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-405881-1.00001-x · Cited by 459 · see citing works
Pathological aspects of lipid peroxidation
Nègre‐Salvayre, A., Augè, N., Ayala, V., Başağa, H., Boada, J., Brenke, R., Chapple, S. J., Cohen, G., Fehér, J., Grune, T., et al. (2010) · Free Radical Research · doi:10.3109/10715762.2010.498478 · Cited by 451 · see citing works
Inactivation of Human Manganese-superoxide Dismutase by Peroxynitrite Is Caused by Exclusive Nitration of Tyrosine 34 to 3-Nitrotyrosine
Yamakura, F., Taka, H., Fujimura, T., & Murayama, K. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.23.14085 · Cited by 442 · see citing works
Reactive Oxygen Species Are Signalling Molecules for Skeletal Muscle Adaptation
Powers, S. K., Duarte, J., Kavazis, A. N., & Talbert, E. E. (2010) · Experimental Physiology · doi:10.1113/expphysiol.2009.050526 · Cited by 440 · see citing works
The Skeletal Muscle Calcium Release Channel
Eu, J. P., Sun, J., Xu, L., Stamler, J. S., & Meissner, G. (2000) · Cell · doi:10.1016/s0092-8674(00)00054-4 · Cited by 434 · see citing works
The challenges of using fluorescent probes to detect and quantify specific reactive oxygen species in living cells
Winterbourn, C. C. (2013) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2013.05.004 · Cited by 420 · see citing works
Analysis of global mRNA expression in human skeletal muscle during recovery from endurance exercise
Mahoney, D. J., Parise, G., Melov, S., Safdar, A., & Tarnopolsky, M. A. (2005) · The FASEB Journal · doi:10.1096/fj.04-3149fje · Cited by 418 · see citing works
Antioxidants: Molecules, medicines, and myths
Gutteridge, J. M. C., & Halliwell, B. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.02.071 · Cited by 405 · see citing works
Nitric oxide represses inhibitory κB kinase through S-nitrosylation
Reynaert, N. L., Ckless, K., Korn, S. H., Vos, N., Guala, A. S., Wouters, E. F. �., van der Vliet, A., & Janssen-Heininger, Y. M. W. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400588101 · Cited by 388 · see citing works
The transcriptional coactivator PGC-1α mediates exercise-induced angiogenesis in skeletal muscle
Chinsomboon, J., Ruas, J., Gupta, R. K., Thom, R., Shoag, J., Rowe, G. C., Sawada, N., Raghuram, S., & Arany, Z. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0909131106 · Cited by 379 · see citing works
Non-Antioxidant Activities of Vitamin E
Zingg, J.-M. A., & Azzi, A. (2004) · Current Medicinal Chemistry · doi:10.2174/0929867043365332 · Cited by 377 · see citing works
Superoxide dismutase in redox biology: the roles of superoxide and hydrogen peroxide
R. Buettner, G. (2011) · Anti-Cancer Agents in Medicinal Chemistry · doi:10.2174/187152011795677544 · Cited by 374 · see citing works
Exercise intensity-dependent regulation of peroxisome proliferator-activated receptor γ coactivator-1α mRNA abundance is associated with differential activation of upstream signalling kinases in human skeletal muscle: Exercise intensity and PGC-1α regulation
Egan, B., Carson, B. P., Garcia-Roves, P. M., Chibalin, A. V., Sarsfield, F. M., Barron, N., McCaffrey, N., Moyna, N. M., Zierath, J. R., & O’Gorman, D. J. (2010) · The Journal of Physiology · doi:10.1113/jphysiol.2010.188011 · Cited by 373 · see citing works
Catalytic mechanisms and specificities of glutathione peroxidases: variations of a basic scheme
Toppo, S., Flohé, L., Ursini, F., Vanin, S., & Maiorino, M. (2009) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2009.04.007 · Cited by 368 · see citing works
Compartmentalization of Redox Signaling Through NADPH Oxidase–Derived ROS
Ushio‐Fukai, M. (2008) · Antioxidants and Redox Signaling · doi:10.1089/ars.2008.2333 · Cited by 365 · see citing works
In Vivo Mapping of Hydrogen Peroxide and Oxidized Glutathione Reveals Chemical and Regional Specificity of Redox Homeostasis
Albrecht, S. C., Barata, A. G., Großhans, J., Teleman, A. A., & Dick, T. P. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.10.010 · Cited by 362 · see citing works
Nitric oxide signaling: Classical, less classical, and nonclassical mechanisms
Martı́nez-Ruiz, A., Cadenas, S., & Lamas, S. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.04.010 · Cited by 336 · see citing works
Vitamin C and E supplementation hampers cellular adaptation to endurance training in humans: a double‐blind, randomised, controlled trial
Paulsen, G., Cumming, K. T., Holden, G., Hallén, J., Rønnestad, B. R., Sveen, O., Skaug, A., Paur, I., Bastani, N. E., Østgaard, H. N., et al. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2013.267419 · Cited by 333 · see citing works
Sites of superoxide and hydrogen peroxide production by muscle mitochondria assessed ex vivo under conditions mimicking rest and exercise
Goncalves, R. L. S., Quinlan, C. L., Perevoshchikova, I. V., Hey-Mogensen, M., & Brand, M. D. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.619072 · Cited by 329 · cited 1× · see citing works
“There are several sources of superoxide in skeletal muscle, including: mitochondrial electr on 151 transport chain complex I and III, NADPH oxidases, dual oxidases, xanthine oxidase, 152 uncoupled NOS isoforms, phospholipases and lipoxyge nas s [57-59].”
Background
The antioxidant paradox: less paradoxical now?
Halliwell, B. (2013) · British Journal of Clinical Pharmacology · doi:10.1111/j.1365-2125.2012.04272.x · Cited by 318 · see citing works
Inactivation of Glutathione Peroxidase by Nitric Oxide
Asahi, M., Fujii, J., Suzuki, K., Seo, H. G., Kuzuya, T., Hori, M., Tada, M., Fujii, S., & Taniguchi, N. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.36.21035 · Cited by 309 · see citing works
Superoxide anion permeability of phospholipid membranes and chloroplast thylakoids
Takahashi, M., & Asada, K. (1983) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(83)90325-9 · Cited by 309 · see citing works
An overview of mechanisms of redox signaling
Forman, H. J., Ursini, F., & Maiorino, M. (2014) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2014.01.018 · Cited by 306 · see citing works
The Redox Biochemistry of Protein Sulfenylation and Sulfinylation
Conte, M. L., & Carroll, K. S. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.r113.467738 · Cited by 305 · see citing works
Even free radicals should follow some rules: A Guide to free radical research terminology and methodology
Forman, H. J., Augusto, O., Brigelius‐Flohé, R., Dennery, P. A., Kalyanaraman, B., Ischiropoulos, H., Mann, G. E., Radí, R., Roberts, L. J., Viña, J., et al. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.10.504 · Cited by 303 · see citing works
Non‐antioxidant molecular functions of α‐tocopherol (vitamin E)
Azzi, A., Ricciarelli, R., & Zingg, J.-M. (2002) · FEBS Letters · doi:10.1016/s0014-5793(02)02706-0 · Cited by 301 · see citing works
Detection of protein S-nitrosylation with the biotin-switch technique
Forrester, M. T., Foster, M. W., Benhar, M., & Stamler, J. S. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2008.09.034 · Cited by 298 · see citing works
The Redox Basis of Epigenetic Modifications: From Mechanisms to Functional Consequences
Cyr, A. R., & Domann, F. E. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3492 · Cited by 294 · see citing works
Modulation of skeletal muscle antioxidant defense by exercise: Role of redox signaling
Ji, L. L. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.02.031 · Cited by 291 · see citing works
The mechanism of catalase action. I. Steady-state analysis
Chance, B., Greenstein, D. S., & Roughton, F. J. W. (1952) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(52)90194-x · Cited by 285 · see citing works
Studies of Mitochondrial and Nonmitochondrial Sources Implicate Nicotinamide Adenine Dinucleotide Phosphate Oxidase(s) in the Increased Skeletal Muscle Superoxide Generation That Occurs During Contractile Activity
Sakellariou, G. K., Vasilaki, A., Palomero, J., Kayani, A., Zibrik, L., McArdle, A., & Jackson, M. J. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4623 · Cited by 276 · see citing works
Nitric oxide and peroxynitrite. The ugly, the uglier and the not so good
Halliwell, B. B., Zhao, K., & Whiteman, M. (1999) · Free Radical Research · doi:10.1080/10715769900301221 · Cited by 275 · see citing works
Regulation of protein function and signaling by reversible cysteine S-nitrosylation
Gould, N., Doulias, P.-T., Tenopoulou, M., Raju, K., & Ischiropoulos, H. (2013) · Journal of Biological Chemistry · doi:10.1074/jbc.r113.460261 · Cited by 274 · see citing works
Effect of Vitamin C Supplements on Antioxidant Defence and Stress Proteins in Human Lymphocytes and Skeletal Muscle
Khassaf, M. B., McArdle, A., Esanu, C., Vasilaki, A., McArdle, F., Griffiths, R. D., Brodie, D. A., & Jackson, M. J. (2003) · The Journal of Physiology · doi:10.1113/jphysiol.2003.040303 · Cited by 273 · see citing works
Mechanisms of S-nitrosothiol formation and selectivity in nitric oxide signaling
Smith, B. C., & Marletta, M. A. (2012) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2012.10.016 · Cited by 270 · see citing works
The Reaction of Superoxide with Reduced Glutathione
Winterbourn, C. C., & Metodiewa, D. (1994) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1994.1444 · Cited by 269 · see citing works
H2O2-induced O⨪2Production by a Non-phagocytic NAD(P)H Oxidase Causes Oxidant Injury
Li, W. G., Miller, F. J., Zhang, H. J., Spitz, D. R., Oberley, L. W., & Weintraub, N. L. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102124200 · Cited by 265 · see citing works
How does ascorbic acid prevent endothelial dysfunction?
May, J. M. (2000) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(00)00269-0 · Cited by 260 · see citing works
S-Nitrosothiols: cellular formation and transport
Zhang, Y., & Hogg, N. (2005) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.12.016 · Cited by 257 · see citing works
Mitochondrial redox signalling at a glance
Collins, Y., Chouchani, E. T., James, A. M., Menger, K. E., Cochemé, H. M., & Murphy, M. P. (2012) · Journal of Cell Science · doi:10.1242/jcs.098475 · Cited by 255 · see citing works
Redox compartmentalization and cellular stress
Jones, D. P., & Go, Y.-M. (2010) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2010.01266.x · Cited by 246 · see citing works
The Exercise-Induced Stress Response of Skeletal Muscle, with Specific Emphasis on Humans
Morton, J. P., Kayani, A. C., McArdle, A., & Drust, B. (2009) · Sports Medicine · doi:10.2165/00007256-200939080-00003 · Cited by 245 · see citing works
Self-citation
Cell culture, oxidative stress, and antioxidants: Avoiding pitfalls
Halliwell, B. B. (2014) · Biomedical Journal · doi:10.4103/2319-4170.128725 · Cited by 222 · see citing works
Prevention of Tocopherol-mediated Peroxidation in Ubiquinol-10-free Human Low Density Lipoprotein
Bowry, V. W., Mohr, D., Cleary, J., & Stocker, R. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.11.5756 · Cited by 212 · see citing works
Human peroxiredoxin 5 is a peroxynitrite reductase
Dubuisson, M., Stricht, D. V., Clippe, A., Etienne, F., Nauser, T., Kissner, R., Koppenol, W. H., Rees, J., & Knoops, B. (2004) · FEBS Letters · doi:10.1016/j.febslet.2004.06.080 · Cited by 212 · see citing works
The production of reactive oxygen and nitrogen species by skeletal muscle
Jackson, M. J., Pye, D., & Palomero, J. (2006) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01102.2006 · Cited by 210 · see citing works
Angiogenesis during exercise and training.
Bloor, C. M. (2005) · Angiogenesis · doi:10.1007/s10456-005-9013-x · Cited by 206 · see citing works
Exercise activation of muscle peroxisome proliferator-activated receptor-γ coactivator-1α signaling is redox sensitive
Kang, C., OʼMoore, K. M., Dickman, J. R., & Ji, L. L. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.08.007 · Cited by 204 · see citing works
Variability in training-induced skeletal muscle adaptation
Timmons, J. A. (2010) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00934.2010 · Cited by 202 · see citing works
Vitamin C and genomic stability
Halliwell, B. B. (2001) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(01)00072-0 · Cited by 201 · see citing works
The physiological role of reversible methionine oxidation
Drazic, A., & Winter, J. (2014) · Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics · doi:10.1016/j.bbapap.2014.01.001 · Cited by 198 · see citing works
4-Hydroxynonenal Induces Adaptive Response and Enhances PC12 Cell Tolerance Primarily through Induction of Thioredoxin Reductase 1 via Activation of Nrf2
Chen, Z.-H., Saito, Y., Yoshida, Y., Sekine, A., Noguchi, N., & Niki, E. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m508556200 · Cited by 197 · see citing works
A Transverse Tubule NADPH Oxidase Activity Stimulates Calcium Release from Isolated Triads via Ryanodine Receptor Type 1 S -Glutathionylation
Hidalgo, C., Sánchez, G., Barrientos, G. C., & Aracena-Parks, P. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600451200 · Cited by 196 · see citing works
Redefining the major contributors to superoxide production in contracting skeletal muscle. The role of NAD(P)H oxidases
Sakellariou, G. K., Jackson, M. J., & Vasilaki, A. (2014) · Free Radical Research · doi:10.3109/10715762.2013.830718 · Cited by 184 · see citing works
Antioxidant Supplementation Does Not Alter Endurance Training Adaptation
Yfanti, C., Akerstrom, T. C. A., Nielsen, S. J., Nielsen, A. R., Mounier, R., Mortensen, O. H., Lykkesfeldt, J., Rose, A. J., Fischer, C. P., & Pedersen, B. K. (2010) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e3181cd76be · Cited by 182 · see citing works
Pre-steady state kinetic characterization of human peroxiredoxin 5: Taking advantage of Trp84 fluorescence increase upon oxidation
Trujillo, M., Clippe, A., Manta, B., Ferrer‐Sueta, G., Smeets, A., Declercq, J., Knoops, B., & Radí, R. (2007) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2007.08.008 · Cited by 179 · see citing works
Vitamin C: poison, prophylactic or panacea?
Halliwell, B. B. (1999) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(99)01418-8 · Cited by 174 · see citing works
Kinetic and mechanistic considerations to assess the biological fate of peroxynitrite
Carballal, S., Bartesaghi, S., & Radí, R. (2013) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2013.07.005 · Cited by 160 · see citing works
S‐nitrosation of Cys‐800 of HIF‐1α protein activates its interaction with p300 and stimulates its transcriptional activity
Yasinska, I. M., & Sumbayev, V. V. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00807-x · Cited by 156 · see citing works
Myotube depolarization generates reactive oxygen species through NAD(P)H oxidase; ROS‐elicited Ca2+ stimulates ERK, CREB, early genes
Espinosa, A., Leiva, A., Peña, M., Müller, M., Anibal Debandi, L., Hidalgo, C., Carrasco, M. A., & Jaimovich, E. (2006) · Journal of Cellular Physiology · doi:10.1002/jcp.20745 · Cited by 155 · see citing works
Free radical biology of the cardiovascular system
Chen, A. F., Chen, D., Daiber, A., Faraci, F. M., Li, H., Rembold, C. M., & Laher, I. (2012) · Clinical Science · doi:10.1042/cs20110562 · Cited by 153 · see citing works
No effect of antioxidant supplementation on muscle performance and blood redox status adaptations to eccentric training
Theodorou, A. A., Nikolaidis, M. G., Paschalis, V., Koutsias, S., Panayiotou, G., Fatouros, I. G., Koutedakis, Y., & Jamurtas, A. Z. (2011) · American Journal of Clinical Nutrition · doi:10.3945/ajcn.110.009266 · Cited by 152 · see citing works
Self-citation
Vitamin C and E supplementation alters protein signalling after a strength training session, but not muscle growth during 10 weeks of training
Paulsen, G., Hamarsland, H., Cumming, K. T., Johansen, R. E., Hulmi, J. J., Børsheim, E., Wiig, H., Garthe, I., & Raastad, T. (2014) · The Journal of Physiology · doi:10.1113/jphysiol.2014.279950 · Cited by 148 · see citing works
Normal adaptations to exercise despite protection against oxidative stress
Higashida, K., Kim, S. H., Higuchi, M., Holloszy, J. O., & Han, D.-H. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00655.2010 · Cited by 148 · see citing works
Antioxidants as therapies: can we improve on nature?
Murphy, M. P. (2013) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2013.04.010 · Cited by 148 · see citing works
Nitration of Hsp90 induces cell death
Franco, M. C., Ye, Y., Refakis, C. A., Feldman, J. L., Stokes, A. L., Basso, M., de Mera, R. M. M.-F., Sparrow, N. A., Calingasan, N. Y., Kiaei, M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1215177110 · Cited by 146 · see citing works
Lipid Rafts and Caveolae and Their Role in Compartmentation of Redox Signaling
Patel, H. H., & Insel, P. A. (2008) · Antioxidants and Redox Signaling · doi:10.1089/ars.2008.2365 · Cited by 139 · see citing works
Regulation of gene expression by α-tocopherol
Azzi, A., Gysin, R., Kempná, P., Munteanu, A., Villacorta, L., Visarius, T. M., & Zingg, J.-M. (2004) · Biological Chemistry · doi:10.1515/bc.2004.072 · Cited by 139 · see citing works
Do antioxidants impair signaling by reactive oxygen species and lipid oxidation products?
Niki, E. (2012) · FEBS Letters · doi:10.1016/j.febslet.2012.09.025 · Cited by 138 · see citing works
Blood as a reactive species generator and redox status regulator during exercise
Nikolaidis, M. G., & Jamurtas, A. Z. (2009) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2009.08.015 · Cited by 136 · see citing works
Self-citation
Low Ascorbate Levels Are Associated with Increased Hypoxia-Inducible Factor-1 Activity and an Aggressive Tumor Phenotype in Endometrial Cancer
Kuiper, C., Molenaar, I. G. M., Dachs, G. U., Currie, M. J., Sykes, P. H., & Vissers, M. C. M. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-0263 · Cited by 135 · see citing works
Inactivation of Glutathione Peroxidase by Peroxynitrite
Padmaja, S., Squadrito, G. L., & Pryor, W. A. (1998) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1997.0407 · Cited by 134 · see citing works
Antioxidants in Sport Nutrition
Lamprecht, M. (2014) · CRC Press eBooks · doi:10.1201/b17442 · Cited by 133 · see citing works
A primer on peroxiredoxin biochemistry
Karplus, P. A. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.10.009 · Cited by 131 · see citing works
Skeletal muscle sarcoplasmic reticulum contains a NADH-dependent oxidase that generates superoxide
Xia, R., Webb, J. A., Gnall, L. L. M., Cutler, K., & Abramson, J. J. (2003) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00034.2002 · Cited by 129 · see citing works
Oxygen-coupled redox regulation of the skeletal muscle ryanodine receptor-Ca 2+ release channel by NADPH oxidase 4
Sun, Q.-A., Hess, D. T., Nogueira, L., Yong, S., Bowles, D. E., Eu, J. P., Laurita, K. R., Meissner, G., & Stamler, J. S. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1109546108 · Cited by 120 · see citing works
Does Vitamin C and E Supplementation Impair the Favorable Adaptations of Regular Exercise?
Nikolaidis, M. G., Kerksick, C. M., Lamprecht, M., & McAnulty, S. R. (2012) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2012/707941 · Cited by 116 · see citing works
Self-citation
Nitric oxide and peroxynitrite
Beckman, J. S. (1993) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(93)90271-u · Cited by 115 · see citing works
In Situ Detection and Measurement of Intracellular Reactive Oxygen Species in Single Isolated Mature Skeletal Muscle Fibers by Real Time Fluorescence Microscopy
Palomero, J., Pye, D., Kabayo, T., Spiller, D. G., & Jackson, M. J. (2008) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.2009 · Cited by 111 · see citing works
Myths, Artifacts, and Fatal Flaws: Identifying Limitations and Opportunities in Vitamin C Research
Michels, A., & Frei, B. (2013) · Nutrients · doi:10.3390/nu5125161 · Cited by 111 · see citing works
Vitamin C improves the quality of somatic cell reprogramming
Esteban, M. A., & Pei, D. (2012) · Nature Genetics · doi:10.1038/ng.2222 · Cited by 109 · see citing works
Reaction of ascorbic acid with S-nitrosothiols: clear evidence for two distinct reaction pathways
Holmes, A. J., & Williams, D. L. H. (2000) · Journal of the Chemical Society Perkin Transactions 2 · doi:10.1039/b004028m · Cited by 108 · see citing works
The Role of Oxidative, Inflammatory and Neuroendocrinological Systems During Exercise Stress in Athletes: Implications of Antioxidant Supplementation on Physiological Adaptation During Intensified Physical Training
Slattery, K., Bentley, D. J., & Coutts, A. J. (2014) · Sports Medicine · doi:10.1007/s40279-014-0282-7 · Cited by 107 · see citing works
An ascorbate-dependent artifact that interferes with the interpretation of the biotin switch assay
Huang, B., & Chen, C. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.03.006 · Cited by 106 · see citing works
Lifelong training preserves some redox-regulated adaptive responses after an acute exercise stimulus in aged human skeletal muscle
Cobley, J. N., Sakellariou, G. K., Owens, D. J., Murray, S. W., Waldron, S., Gregson, W. A., Fraser, W. D., Burniston, J. G., Iwanejko, L., McArdle, A., et al. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.02.004 · Cited by 105 · see citing works
Self-citation
Low vitamin C values are linked with decreased physical performance and increased oxidative stress: reversal by vitamin C supplementation
Paschalis, V., Theodorou, A. A., Kyparos, A., Dipla, K., Zafeiridis, A., Panayiotou, G., Vrabas, I. S., & Nikolaidis, M. G. (2016) · European Journal of Nutrition · doi:10.1007/s00394-014-0821-x · Cited by 103 · see citing works
Self-citation
The Basic Biology of Redoxosomes in Cytokine-Mediated Signal Transduction and Implications for Disease-Specific Therapies
Spencer, N. Y., & Engelhardt, J. F. (2014) · Biochemistry · doi:10.1021/bi401719r · Cited by 98 · see citing works
Real‐time measurement of nitric oxide in single mature mouse skeletal muscle fibres during contractions
Pye, D., Palomero, J., Kabayo, T., & Jackson, M. J. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2006.125930 · Cited by 96 · see citing works
Oxidation of tetrahydrobiopterin by biological radicals and scavenging of the trihydrobiopterin radical by ascorbate
Patel, K. B., Stratford, M. R. L., Wardman, P., & Everett, S. A. (2002) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(01)00777-8 · Cited by 95 · see citing works
Natural Forms of Vitamin E and 13′-Carboxychromanol, a Long-Chain Vitamin E Metabolite, Inhibit Leukotriene Generation from Stimulated Neutrophils by Blocking Calcium Influx and Suppressing 5-Lipoxygenase Activity, Respectively
Jiang, Z., Yin, X., & Jiang, Q. (2010) · The Journal of Immunology · doi:10.4049/jimmunol.1002342 · Cited by 93 · see citing works
Human skeletal muscle ascorbate is highly responsive to changes in vitamin C intake and plasma concentrations
Carr, A. C., Bozonet, S. M., Pullar, J. M., Simcock, J. W., & Vissers, M. C. (2013) · The American Journal of Clinical Nutrition · doi:10.3945/ajcn.112.053207 · Cited by 88 · see citing works
Reductive stress after exercise: The issue of redox individuality
Margaritelis, N., Kyparos, A., Paschalis, V., Theodorou, A., Panayiotou, G., Zafeiridis, A., Dipla, K., Nikolaidis, M., & Vrabas, I. (2014) · Redox Biology · doi:10.1016/j.redox.2014.02.003 · Cited by 86 · see citing works
Self-citation
Cytosolic Peroxiredoxin Attenuates The Activation Of Jnk And P38 But Potentiates That Of Erk In Hela Cells Stimulated With Tumor Necrosis Factor-α
Kang, S. W., Chang, T.-S., Lee, T., Kim, E. S., Yu, D., & Rhee, S. G. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m307698200 · Cited by 85 · see citing works
Effect of antioxidant supplementation on insulin sensitivity in response to endurance exercise training
Yfanti, C., Nielsen, A. R., Åkerström, T., Nielsen, S., Rose, A. J., Richter, E. A., Lykkesfeldt, J., Fischer, C. P., & Pedersen, B. K. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00207.2010 · Cited by 85 · see citing works
Dietary Antioxidants as Modifiers of Physiologic Adaptations to Exercise
MANKOWSKI, R. T., ANTON, S. D., BUFORD, T. W., & LEEUWENBURGH, C. (2015) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0000000000000620 · Cited by 83 · see citing works
N-acetylcysteine’s attenuation of fatigue after repeated bouts of intermittent exercise: practical implications for tournament situations
Cobley, J. N., McGlory, C., Morton, J. P., & Close, G. L. (2011) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.21.6.451 · Cited by 76 · see citing works
Self-citation
Role of superoxide–nitric oxide interactions in the accelerated age‐related loss of muscle mass in mice lacking Cu,Zn superoxide dismutase
Sakellariou, G. K., Pye, D., Vasilaki, A., Zibrik, L., Palomero, J., Kabayo, T., McArdle, F., Remmen, H. V., Richardson, A. G., Tidball, J. G., et al. (2011) · Aging Cell · doi:10.1111/j.1474-9726.2011.00709.x · Cited by 75 · see citing works
Induction of Adaptive Response and Enhancement of PC12 Cell Tolerance by 7-Hydroxycholesterol and 15-Deoxy-Δ12,14-Prostaglandin J2 through Up-regulation of Cellular Glutathione via Different Mechanisms
Chen, Z.-H., Yoshida, Y., Saito, Y., Sekine, A., Noguchi, N., & Niki, E. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600260200 · Cited by 73 · see citing works
Comparison between Glucose-6-Phosphate Dehydrogenase-Deficient and Normal Individuals after Eccentric Exercise
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Self-citation
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The Skeletal Muscle
Sjöstróm, M. (1980) · Palgrave Macmillan UK eBooks · doi:10.1007/978-1-349-06174-7_7 · Cited by 23 · see citing works
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Self-citation
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Flagged first, then by citations

Research works printed but not linked: 2

Winterbourn, C.C. Are free radicals involved in thiol-based redox signalling? Free Radic Biol Med. http://dx.doi.org/10.1016/j.freeradbiolmed.2014.08.017i; 2014. · DOI
Halliwell, B.; Gutteridge, J.M.C. Free Radicals in Biology & Medicine. Fourth Edition. Oxford University Press: Oxford; 2007.

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Authors: Cobley, J. N., McHardy, H., Morton, J. P., Nikolaidis, M. G., & Close, G. L.
Affiliations: Abertay University (GB)
Liverpool John Moores University (GB)
Aristotle University of Thessaloniki (GR)
Corresponding author: Cobley, James N.
ORCID: Cobley, James N.
Morton, James P.
Nikolaidis, Michalis G.
Close, Graeme L.
Venue: Free Radical Biology and Medicine
Publisher: Elsevier BV
Published: 2015-07
Volume: 84
Pages: 65-76
ISSN: 0891-5849 (ISSN-L)
DOI: 10.1016/j.freeradbiomed.2015.03.018
OpenAlex: W2016974821
Cited by: 118
References: 202
Citations by year: 2026: 1 · 2025: 9 · 2024: 10 · 2023: 8 · 2022: 9 · 2021: 11 · 2020: 17 · 2019: 11 · 2018: 13 · 2017: 12 · 2016: 11 · 2015: 4 · 2014: 2
FWCI: 1.85
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Free Radical Biology and Medicine (publishedVersion)
PubMed (publishedVersion)
Discovery Research Portal (University of Dundee) (submittedVersion)
Abertay Research Portal (Abertay University) (submittedVersion, cc-by-nc-nd)
Funders: Carnegie Trust (R70103)
Topics: Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
Health Sciences › Medicine › Biochemistry › Antioxidant Activity and Oxidative Stress
Health Sciences › Nursing › Nutrition and Dietetics › Vitamin C and Antioxidants Research
Keywords: vitamin C, vitamin E, alpha-tocopherol, redox signaling, exercise adaptation, reactive oxygen species, reactive nitrogen species, superoxide, hydrogen peroxide, nitric oxide signaling, peroxynitrite, NADPH oxidase, superoxide dismutase, antioxidants
MeSH terms: Adaptation, Physiological, Animals, Antioxidants, Ascorbic Acid, Humans, Oxidation-Reduction, Vitamin E, Signal Transduction, Exercise, Reactive Oxygen Species, Oxidative Stress, Reactive Nitrogen Species

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Influence of vitamin C and vitamin E on redox signaling: implications for exercise adaptations

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