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Michalis G. Nikolaidis_ECSS Vienna 2016
- 1. FUNDAMENTAL AND EMERGING CONCEPTS IN THE REDOX REGULATION OF EXERCISE RESPONSES AND ADAPTATIONS Michalis G. Nikolaidis Department of Physical Education and Sports Science (Serres) Aristotle University of Thessaloniki Greece nikolaidis@auth.gr nikolaidis.weebly.com Trying to bring some order to chaos
- 2. Trying to bring some order to chaos
- 3. INVOLVEMENT of reactive species in exercise responses and adaptations F C I FUNDAMENTALITY of redox reactions in biology COMPLEXITY of reactive species metabolism I would argue for:
- 4. F I would argue for: INVOLVEMENT of reactive species in exercise responses and adaptations F C I FUNDAMENTALITY of redox reactions in biology COMPLEXITY of reactive species metabolism
- 5. C I would argue for: INVOLVEMENT of reactive species in exercise responses and adaptations F C I FUNDAMENTALITY of redox reactions in biology COMPLEXITY of reactive species metabolism
- 6. I I would argue for: INVOLVEMENT of reactive species in exercise responses and adaptations F C I FUNDAMENTALITY of redox reactions in biology COMPLEXITY of reactive species metabolism
- 7. OH• H2O2 10-12 s O2 •- 10-6 s min ROO• 2 s NO• 30 s HClO s to min C Increasing half life Heterogeneity of reactive species
- 8. Heterogeneity of antioxidants C Cell SOD_3 SOD_1 SOD_1 SOD_2 V C V C V C V C
- 9. Architectural and functional specificity of redox metabolism
- 10. H2O2 Prx-2red STAT3red H2O Prx-2ox STAT3ox Redox signaling H2O2 Prx-2overox (inactive) Target protein Random oxidations Redox signaling Oxidative stress F C Cell signaling via redox molecules H2O2 H2O2 H2O
- 11. Plasma membrane Sarcoplasmic reticulum Ryanodine receptor Place et al. PNAS 112:15492, 2015 MDA Ca2+ F C I Responses/adaptations to oxidative stress
- 12. CuZnSOD Plasma membrane Endothelium ecSOD H2O2 nNOS Sarcoplasmic reticulum T-tubule Mitochondrion H2O2 MnSOD H2O2 NADPH oxidase Phospholipase A2 XO NADPH oxidase NADPH oxidase eNOSETC Based on data from Sakellariou et al. Free Radic Res 48:12, 2014 O2 − O2 − O2 − C Exercise produces reactive species
- 13. What is the role of reactive species and oxidative stress after exercise?
- 14. I The conventional approach Rest Reactive species Cobley et al. Free Radic Biol Med 84:65, 2015
- 15. Reactive species I The conventional approach Exercise Antioxidant supplementation Responses and adaptations Cobley et al. Free Radic Biol Med 84:65, 2015
- 16. Gomez-Cabrera et al. Am J Clin Nutr 87:142, 2008Gomez-Cabrera et al. J Physiol 567:113, 2005 NF-κB(au) 12 6 3 0 9 Untrained Trained Trained Allopurinol Endurance(%) Trained Trained Vitamin C 25 10 5 0 15 20 F I A milestone
- 17. 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
- 18. TAP PI3-kinase (active) Azzi et al. Arch Biochem Biophys 595:100, 2016 Vit E OH PI3-kinase (inactive) Redox active TAP Vit E OH F C Non-antioxidant effects of antioxidants TAP Vit E OH Redox inactive PI3-kinase (inactive)
- 19. Margaritelis et al. Redox Biol 2:520, 2014 0% 12% 100% Oxidative stress Reductive stress C Redox individuality
- 20. Paschalis et al. Eur J Nutr 55:45, 2016 I Personalized antioxidant supplementation High vitamin C (n=10) Low vitamin C (n=10) 60 days Wash out 30 days 30 days Placebo Vitamin C Placebo Vitamin C Placebo Vitamin C Placebo Vitamin C n = 100
- 21. VO2max(ml/kg/min) Paschalis et al. Eur J Nutr 55:45, 2016 VitaminC(μmol/L) 20 40 60 80 0 I Beneficial effects of Vit C on the ‘rancid’F2-isoprostanes(pg/mgcr.) 100 Pre supplementation Post supplementation 200 400 600 0 800 Pre supplementation Post supplementation 15 30 45 0 60 Pre supplementation Post supplementation High vitamin C group Low vitamin C group
- 22. Margaritelis et al. under review 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 n=100 Stratification and regression to the mean
- 23. -40 -20 0 20 40 60 80 100 120 140 F2-isoprostanes(%change) 1st trial 2nd trial 1st trial 2nd trial High EIOS Moderate EIOS 1st trial 2nd trial Low EIOS Margaritelis et al. under review Verification of regression to the mean
- 24. Margaritelis et al. under review 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 n=100 The role of oxidative stress in adaptations Time (weeks) 0 Cycling training 3 6 Redox & Performance Redox & Performance
- 25. VO2max (% change) Low EIOS Moderate EIOS High EIOS 5 10 15 20 Time trial (% change) 10 20 30 Margaritelis et al. under review 00 I Low oxidative stress leads to low adaptations Low EIOS Moderate EIOS High EIOS a ‘free radical’ supplement
- 26. Veskoukis et al. under review NADP+ NADPH GRred GRox GSH GSSG GPxred GPxox H2O + O2 CAT, GST O2 •- SOD H2O2TrxRox TrxRred Prxox Prxred Trxred Trxox H2O2 Prxoverox SrxL-arginine NOS NO• NADPH oxidase F C Centrality of NADPH in redox regulation
- 27. Time to exhaustion (s) Exercise Exercise Nicotinamide riboside 40 80 120 160 Kourtzidis et al. under review 0 I Nicotinamide riboside: an NADPH booster
- 29. Acknowledgements Antonios Kyparos Aristidis Veskoukis Nikos Margaritelis Aristotle University of Thessaloniki, Greece Vassilis Paschalis University of Thessaly, Greece Anastasios Theodorou European University, Cyprus