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Trying to bring some order to chaos
FUNDAMENTAL AND EMERGING CONCEPTS IN THE REDOX REGULATION OF EXERCISE RESPONSES AND ADAPTATIONS Trying to bring some order to chaos Michalis G. Nikolaidis Department of Physical Education and Sports Science (Serres) Aristotle University of Thessaloniki Greece nikolaidis.weebly.com
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Trying to bring some order to chaos
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F C I I would argue for: FUNDAMENTALITY of redox reactions in biology
COMPLEXITY of reactive species metabolism INVOLVEMENT of reactive species in exercise responses and adaptations I
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F C I I would argue for: F C I
FUNDAMENTALITY of redox reactions in biology C COMPLEXITY of reactive species metabolism INVOLVEMENT of reactive species in exercise responses and adaptations I
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F C I I would argue for: F C I
FUNDAMENTALITY of redox reactions in biology C COMPLEXITY of reactive species metabolism INVOLVEMENT of reactive species in exercise responses and adaptations I
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F C I I would argue for: F C I
FUNDAMENTALITY of redox reactions in biology C COMPLEXITY of reactive species metabolism INVOLVEMENT of reactive species in exercise responses and adaptations I
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Heterogeneity of reactive species
s to min min OH• O2•- ROO• NO• HClO H2O2 Increasing half life
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Heterogeneity of antioxidants
C I SOD_3 VC SOD_1 VC SOD_2 VC SOD_1 VC Cell
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Architectural and functional specificity
of redox metabolism
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Cell signaling via redox molecules
F C I H2O2 Prx-2red STAT3ox Redox signaling H2O Prx-2ox STAT3red H2O2 Target protein H2O2 Redox signaling H2O Random oxidations H2O2 Oxidative stress Prx-2overox (inactive)
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Responses/adaptations to oxidative stress
F C I Plasma membrane MDA Ryanodine receptor Ca2+ Sarcoplasmic reticulum Place et al. PNAS 112:15492, 2015
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Exercise produces reactive species
F C I O2 − ecSOD H2O2 XO Endothelium Plasma membrane nNOS NADPH oxidase T-tubule O2 − NADPH oxidase Sarcoplasmic reticulum CuZnSOD NADPH oxidase H2O2 Phospholipase A2 ETC eNOS O2 − MnSOD H2O2 Mitochondrion Based on data from Sakellariou et al. Free Radic Res 48:12, 2014
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What is the role of reactive species and oxidative stress after exercise?
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The conventional approach
F C I Rest Reactive species Exercise Cobley et al. Free Radic Biol Med 84:65, 2015
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The conventional approach
F C I Rest Responses and adaptations Reactive species Exercise Antioxidant supplementation Cobley et al. Free Radic Biol Med 84:65, 2015
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A milestone F C I Gomez-Cabrera et al. J Physiol 567:113, 2005
12 25 20 9 15 NF-κB (au) 6 Endurance (%) 10 3 5 Untrained Trained Trained Allopurinol Trained Trained Vitamin C Gomez-Cabrera et al. J Physiol 567:113, 2005 Gomez-Cabrera et al. Am J Clin Nutr 87:142, 2008
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Antioxidant supplementation either does not augment or hampers
exercise adaptations “Too much of a good thing” * * Bartlett et al. Eur J Sport Sci 15:3, 2015
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Non-antioxidant effects of antioxidants
Redox active Redox inactive Vit E OH Vit E OH Vit E OH TAP TAP TAP PI3-kinase (inactive) PI3-kinase (inactive) PI3-kinase (active) Azzi et al. Arch Biochem Biophys 595:100, 2016
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Redox individuality F C I Oxidative stress Reductive stress 0% 12%
100% Margaritelis et al. Redox Biol 2:520, 2014
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Personalized antioxidant supplementation
F C I Placebo Placebo High vitamin C (n=10) Vitamin C Vitamin C n = 100 Placebo Placebo Low vitamin C (n=10) Vitamin C Vitamin C 30 days 60 days Wash out 30 days Paschalis et al. Eur J Nutr 55:45, 2016
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Beneficial effects of Vit C on the ‘rancid’
100 80 High vitamin C group 60 Vitamin C (μmol/L) 40 Low vitamin C group 20 Pre supplementation Post supplementation 800 60 600 45 F2-isoprostanes (pg/mg cr.) 400 VO2max (ml/kg/min ) 30 200 15 Pre supplementation Post supplementation Pre supplementation Post supplementation Paschalis et al. Eur J Nutr 55:45, 2016
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Stratification and regression to the mean
1st exercise trial Low EIOS F2-Isop change n=12 Moderate EIOS F2-Isop change n=12 High EIOS F2-Isop change n=12 2nd exercise trial Margaritelis et al. under review
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Verification of regression to the mean
F2-isoprostanes (% change) 1st trial 2nd trial 1st trial 2nd trial 1st trial 2nd trial High EIOS Moderate EIOS Low EIOS Margaritelis et al. under review
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The role of oxidative stress in adaptations
1st exercise trial Low EIOS F2-Isop change n=12 Moderate EIOS F2-Isop change n=12 High EIOS F2-Isop change n=12 2nd exercise trial Redox & Performance Redox & Performance Cycling training 3 6 Time (weeks) Margaritelis et al. under review
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Low oxidative stress leads to low adaptations
F C I Low EIOS Low EIOS Moderate EIOS Moderate EIOS High EIOS High EIOS 5 10 15 20 10 20 30 VO2max (% change) Time trial (% change) a ‘free radical’ supplement Margaritelis et al. under review
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Centrality of NADPH in redox regulation
Veskoukis et al. under review
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Nicotinamide riboside: an NADPH booster
F C I Exercise Exercise Nicotinamide riboside 40 80 120 160 Time to exhaustion (s) Kourtzidis et al. under review
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Conclusion F C I undamentality omplexity nvolvement
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Acknowledgements Antonios Kyparos Aristidis Veskoukis
Nikos Margaritelis Aristotle University of Thessaloniki, Greece Vassilis Paschalis University of Thessaly, Greece Anastasios Theodorou European University, Cyprus
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