exercise and oxidative stress

Question 1

oxidative stress

Answer 1

classical- a disturbance in the prooxidant-antioxidant balance in favour of the former
contemporary- an imbalance between oxidants and antioxidants in favour of the oxidants leading to a disruption in redox signalling, control and/or damage

some degree of oxidants in the body is good but too much antioxidant supplementation can lead to some cancers, CVD etc

Question 2

prooxidants

Answer 2

lead to increased oxidant reactions by indcuing oxidative stress
free radical- an atom or molecules that contains one or more unpaired electron in its outer oribital
thos makes these atoms/molecules highly reactive meaning they can oxidise or nitrate (damage) other molecules such as proteins, lipids and DNA

Question 3

reactive oxygen species

Answer 3

ROS is a general term that refers to oxygen centred free radicals and reactive derivatives of oxygen
these oxidants can lead to oxidative stress, leading to damage of cells/ muscles
incl superoxide, peroxide, hydrogen peroxide, hydroxyl radical, hydroxyl ion

Question 4

superoxide

Answer 4

superoxide is cleaned up by SOD (superoxide dismutase) which combines 2 superoxide molecules to form H2O2
H2O2 isnt ROS but can react with metals to form hydroxyl radicals which is extremely dangerous
H2O2 can also form peroxides to form hydroxyl radical

Question 5

ROS and exercise

Answer 5

ROS is general term that refers to oxygen centred free radicals
some prod of ROS beneficial to help
ROS production is substantially increased during exercise

Question 6

studies

Answer 6

problems are that ROS have very short half life as they are highly reactive
intramuscular ROS prod is increased during repeated skeletal muscle contractions
study results in notes

Question 7

sources of ROS

Answer 7

mitochondria important for producing ROS at rest but they are not as involved during exercise- not main source of ROS as they are very efficient during exercise
produced by 3 main enzymes in the skeletal muscle- NADPH oxidase, xanthine oxidase and PLA2
PLA2- phospholipiase can stimulate ROS production in the mitochondria, cytosol and via NADPH and lipogenesis

Question 8

limitations of increased ROS prod

Answer 8

excessive ROS production can damage lipids, proteins and DNA and has been linked to skeletal muscle fatigue and compromised exercise performance
linked to fatigue during exercise

diabetics would have much larger amount of ROS

Question 9

targets of ROS action in muscle

Answer 9

ROS can damage sarcoplasmic reticulum
can damage proteins such as myosin, actin, tropomyosin, troponin- less likley to bind myosin
animal evidence to show less able to bind calcium and use it to generate force as ROS increase (in humans- sodium potassium pump is sensitive to oxidative stress)
can interfere with lipid membrane on mitochondria
NaK+ pump has been found to be compromised by ROS
nitric oxide- superoxide can react with this and reduce the amount of NO, compromising vasodilation (blood flow) –> turns NO into peroxynitrite (ONOO-)- damaging to tissue

Question 9

mechanisms of ROS action

Answer 9

protein thiol oxidation
cystine - amimno acid- can undergo oxidative modification- due to a certain residue (sulhydryl group) - most proteins have cystine and sulfhydryl
when ROS bind to the thiol (sulhydryl) , it forms a disulphide bond which modified the protein structure and function- can no longer bind to its target
impact on mitochondria, sarcoplasmic reticulum and proteins

Question 9

implications of increased ROS action- negative and positive

Answer 9

has been interpreted to have negative effects on skeletal blood flow, contractile function and exercise capacity

however this is changing from the idea that all ROS are bad
- studies found increase in ROS can increase blood flow during exercise
- vasodilation can be driven by oxidants in young healthy individuals- only a small amount of ROS though
- but this is not the same for disables individuals as they already have a lower abiloty for vasodilation so ROS is not beneficial for them

Question 10

effects on ROS and muscle force

Answer 10

small increase in ROS can increase muscle force production
larger increase in ROS can decrease muscle force production
producing too many oxidants will start to result in the damage- not good in high intensity, sustained exercise

optimal level, producing the most isometric force is in the middle of the oxidation and reduction rates- high ROS levels will lead to high levels of oxidation in cells, decreasing isometric muscle force
graph in notes

Question 11

implications of increased ROS production

Answer 11

antioxidants
diabetics - have lower levels of antioxidants and higher levels oxidants

Question 12

antioxidants

Answer 12

a molecule or enzyme that stabilised volatile and unstable free radicals by donating an electron to derivatives of oxygen
converts free radical oxygen to a stable molecule

Question 13

antioxidant defence

Answer 13

enzymatic
-superoxide dismutase
- catalase (cat)
- glutathionine peroxidase (GPX)
non enzymatic
- glutathionine + cystine- amino acids
- vitamin C and E
- a-lipoic acid

Question 14

importance of endogenous antioxidant enzymes

Answer 14

superoxide can be converted into hydrogen peroxide by SAD
hydorgen peroxide- want to get rid of this -by converting it to water- before it forms hydroxyl radical
glutathione peroxidase- uses glutathione as the electron donor, converting hydrogen peroxide to water

Question 15

regulating enzymes

Answer 15

1. KEAP1 binds to NRF2 in the cell cytosol
2. the bond between KEAP1 and NRF2 can undergo oxidative modification in the presence of increased ROS (oxidative stress will break the bond)
3. releases NRF2 which migrates to the nucleus
4. NRF2 binds to the antioxidant response elements (ARE) which activates the genes that encode for the synthesis on antioxidant enzymes
5. increased cellular content of antixoidant enzymes
   this process will minimise oxidative stress

Question 16

balance

Answer 16

oxidant/ antioxidant balance in resting healthy muscle vs influence of infection or disease
resting= balance between oxidant and antioxidant
intense- greater oxidant than antioxidant

Question 17

shifting the redox balance

Answer 17

looking to delay the negative effects of oxidants on the body
interest in interventions which directly confer or indirectly promote antioxidant responses in the muscle to offset exercise induced oxidative stress and improve exercise performance

Question 18

study- training and enzymes

Answer 18

effect of exercise training on skeletal muscle antioxidant enzymes
- antioxidant status and lipid perioxidation aftr short term maximal exercise in trained and untrained humans
- in endutance training; increases enzymatic antioxidants + reduces oxidants
- less evidence on HIIT and resistance rtraining but dont need as many antioxidants as it is not sustained for long so less effect of oxidants in first palce

Question 19

study- KEAP1 and NRF2 pathway

Answer 19

effect of exercise
- increase in ratio between KEAP1 + NRF2
- pathway is activated mroe during exercise
- leads to increased synthesis of catalse, offsetting oxidative stress that occurs during exercise
- can look specifically in the nucleus rather than just general muscle

Question 20

importance of GSH

Answer 20

glutathione
GSH is a potent antioxidant
can react directly with a varity of ROS by H+ donation
serves as substrate for GPX
it is used to reduce other antioxidants (Vit A and C)
supplementation with lipoic acid, which can support GSH synthesis and lower exercise induced oxidative stress doest improve performance
direct GSH supplementation not an effective strategy to increase muscle GSH and exercise performance

Question 21

NAC

Answer 21

n acetylcysteine administration
antioxidant properties of this are 2 fold- can directly scavenge and can support GSH synthesis
GSH is synthesised from 3 amino acids- glutamate, glycine and cysteine by y glutamyl cysteine syntheatse
cysteine is rate limiting for GSH synthesis

Question 22

antioxidant supplementation

Answer 22

exercise induced ROS prod activates signalling cascades that are integral to allow skeletal muscle to adapt to exercise stimuli
excessive antioxidant supplementation during training is not advised
ensure good antioxidant intake - fruit and veg and protein (cysteine)

taking excess antioxidant during training periods, reducing ROS production could potentially switch off PGC1-a which controls mitochondrial biogenesis so can be detrimental to performance

Question 23

free radicals

Answer 23

an atom or molecules that contains one or more unpaired electron in its outer oribital
thos makes these atoms/molecules highly reactive meaning they can oxidise or nitrate (damage) other molecules such as proteins, lipids and DNA