Transcript
FUNDAMENTAL AND EMERGING CONCEPTS IN THE REDOX REGULATION OF EXERCISE RESPONSES AND ADAPTATIONS
Michalis G. NikolaidisDepartment of Physical Education and Sports Science (Serres)Aristotle University of ThessalonikiGreece
nikolaidis@auth.grnikolaidis.weebly.com
Trying to bring some order to chaos
Trying to bring some order to chaos
INVOLVEMENT of reactive species in exercise responses and adaptations
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C
I
FUNDAMENTALITY of redox reactions in biology
COMPLEXITY of reactive species metabolism
I would argue for:
F C 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
F C 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
F C 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
OH• H2O2
10-12 sO2
•-
10-6 s minROO•
2 sNO•
30 sHClO
s to min
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Increasing half life
Heterogeneity of reactive species
Heterogeneity of antioxidantsF C I
Cell
SOD_3
SOD_1
SOD_1 SOD_2
VC
VC
VC
VC
Architectural and functional specificityof redox metabolism
H2O2 Prx-2red
STAT3redH2O Prx-2ox
STAT3ox Redox signaling
H2O2
Prx-2overox(inactive)
Target protein
Random oxidations
Redox signaling
Oxidative stress
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Cell signaling via redox molecules
H2O2
H2O2
H2O
Plasma membrane
Sarcoplasmic reticulum
Ryanodine receptor
Place et al. PNAS 112:15492, 2015
MDA
Ca2+
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Responses/adaptations to oxidative stress
CuZnSOD
Plasma membrane
Endothelium
ecSOD H2O2
nNOS
Sarcoplasmic reticulum
T-tubule
Mitochondrion
H2O2
MnSOD H2O2
NADPHoxidas
e
Phospholipase A2
XO
NADPHoxidas
e
NADPHoxidas
e
eNOSETC
Based on data from Sakellariou et al. Free Radic Res 48:12, 2014
O2−
O2−
O2−
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Exercise produces reactive species
What is the role of reactive species and oxidative stress after exercise?
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The conventional approach
Exercise
Rest
Reactive species
Cobley et al. Free Radic Biol Med 84:65, 2015
Reactive species
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The conventional approach
Exercise
Rest
Antioxidant supplementation
Responses and adaptations
Cobley et al. Free Radic Biol Med 84:65, 2015
Gomez-Cabrera et al. Am J Clin Nutr 87:142, 2008Gomez-Cabrera et al. J Physiol 567:113, 2005
NF-κ
B (a
u)
12
6
3
0
9
Untrained Trained TrainedAllopurinol
Endu
ranc
e (%
)
Trained TrainedVitamin C
25
10
50
15
20
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A milestone
Antioxidant supplementation eitherdoes not augment or hampers
exercise adaptations
“Too much of a good thing” *
* Bartlett et al. Eur J Sport Sci 15:3, 2015
TAPPI3-kinase
(active)
Azzi et al. Arch Biochem Biophys 595:100, 2016
Vit EOH
PI3-kinase(inactive)
Redox active
TAPVit E
OH
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Non-antioxidant effects of antioxidants
TAPVit E
OH
Redox inactive
PI3-kinase(inactive)
Margaritelis et al. Redox Biol 2:520, 2014
0% 12% 100%
Oxidative stress
Reductive stress
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Redox individuality
Paschalis et al. Eur J Nutr 55:45, 2016
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Personalized antioxidant supplementation
High vitamin C
(n=10)
Low vitamin C (n=10)
60 daysWash out
30 days 30 days
Placebo
Vitamin C
Placebo
Vitamin C
Placebo
Vitamin C
Placebo
Vitamin C
n = 100
VO2m
ax (m
l/kg/
min
)
Paschalis et al. Eur J Nutr 55:45, 2016
Vita
min
C (μ
mol
/L)
20
40
60
80
0
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Beneficial effects of Vit C on the ‘rancid’
F 2-is
opro
stan
es (p
g/m
g cr
.)
100
Presupplementation
Postsupplementation
200
400
600
0
800
Presupplementation
Postsupplementation
15
30
45
0
60
Presupplementation
Postsupplementation
High vitamin C group
Low vitamin C group
Margaritelis et al. under review
1st exercise trial
Low EIOSF2-Isop change
n=12
Moderate EIOS
F2-Isop changen=12
High EIOSF2-Isop change
n=12
2nd exercise trial
n=100
Stratification and regression to the mean
-40
-20
0
20
40
60
80
100
120
140
F 2-is
opro
stan
es (%
cha
nge)
1st trial 2nd trial 1st trial 2nd trialHigh EIOS Moderate EIOS
1st trial 2nd trialLow EIOS
Margaritelis et al. under review
Verification of regression to the mean
Margaritelis et al. under review
1st exercise trial
Low EIOSF2-Isop change
n=12
Moderate EIOS
F2-Isop changen=12
High EIOSF2-Isop change
n=12
2nd exercise trial
n=100
The role of oxidative stress in adaptations
Time (weeks)0
Cycling training3 6
Redox &Performanc
e
Redox &Performanc
e
VO2max (% change)
Low EIOS
Moderate EIOS
High EIOS
5 10 15 20
Time trial (% change)
10 20 30
Margaritelis et al. under review
00
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Low oxidative stress leads to low adaptations
Low EIOS
Moderate EIOS
High EIOS
a ‘free radical’ supplement
Veskoukis et al. under review
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Centrality of NADPH in redox regulation
Time to exhaustion (s)
Exercise
ExerciseNicotinamide riboside
40 80 120 160
Kourtzidis et al. under review
0
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Nicotinamide riboside: an NADPH booster
Fundamentality Complexity Involvement
Conclusion
Acknowledgements
Antonios KyparosAristidis VeskoukisNikos MargaritelisAristotle University of Thessaloniki, Greece
Vassilis PaschalisUniversity of Thessaly, Greece
Anastasios TheodorouEuropean University, Cyprus
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