Free Radicals 2 Flashcards
What are the benefits of free radicals in muscles
Maintaining skeletal muscle structure, function and adaptation
How does exercise increase free radical production
Increased O2 consumption lowers O2 tension intracellularly during exercise which can increase ROS production
Increases in temperature - stimulate free radical production
Decreases in pH can stimulate free radical production
How does NADPH oxidase produce free radicals
Generates superoxide (O2-) by transferring electrons
from NADPH to molecular oxygen.
Superoxide may influence calcium release by sarcoplasmic reticulum
via oxidation of the ryanodine receptor
What is phospholipase A2
An enzyme that cleaves membrane phospholipids to release arachidonic acid.
Give 2 methods of how phospholipase A2 produce free radicals
So there are calcium-dependent (contraction) and independent (relaxation) forms of phospholipase A2.
As PLA2 releases arachidonic acid, AA is used as a substrate for making enzyme systems (lipoxygenases), these generate free radicals
PLA2 can activate NAPDH oxidases which stimulate free radical production in the mitochondria and release into the extracellular space
How does xanthine oxidase produce free radicals
XO oxidises hypoxanthine to xanthine and produces superoxide
Present in skeletal muscles and endothelial cells
Particularly important in ischaemia reperfusion injury.
What role do free radicals have in muscle contraction
Appear to be required to produce normal muscle contraction - the balance between reduction and oxidization is key for optimal muscle contraction
Why are free radicals needed for muscle contraction
Increase opening of sarcoplasmic reticulum calcium release channels and inhibit calcium-dependent ATPase (both increase calcium in contracting muscle)
What did hydrogen peroxide (free radical) type help muscle contraction
No change in levels but increase in calcium sensitivity in myofilaments
What is the role of antioxidants in muscle contraction
Delay muscle fatigue during submaximal contractions
Shown with N-acetylcholine but not all studies show this, especially not during maximal contractions or with vitamin C or E antioxidants
What do very high levels of antioxidants do to muscle contraction strength?
Coombes 2001
Depress it - rat muscle was given very high doses of vitamin E and had lower contractile strength compared to its control counterparts
Showing that there is an optimal level for antioxidants (bell curve-like distribution)
Why do high levels of antioxidants decrease muscle contraction force
These high levels in sarcoplasmic reticulum membranes may lead to a reduction of regulatory sulfhydryl on ryanodine sensitive calcium release channels –> decrease in calcium –> decrease force
How do free radicals help muscles adapt
Cultured myocytes increase gene expression in response to hydrogen peroxide
What role does calorie resitriction have in free radical production
WIDER READING - Fontana 2010
Calorie restriction decreases IGF-1, where SOD (antioxidant) is believed to be involved in its inhibition.
IGF-1 - could be responsible for the reduced spontaneous mutation frequency in the kidney and small intestine of GH deficient and dietary restricted mice and also an increase in malignancy
What is different about the source of ROS when comparing exercise and inactive free radical production
WIDER READING - Powers et al. 2011
recent data indicate that inactivity leads to increased mitochondral ROS production, whereas the ROS produced during exercise seem to originate mostly from non-mitochondrial sources.
What role do free radicals have in muscle atrophy
WIDER READING - (Pellegrino et al. 2011)
In diaphragmatic atrophy (caused by mechanical ventilation) - protein and lipid peroxidation and impairment in the antioxidant defence systems occur.
Slow atrophy - ROS unlikely to play a role as shown by bed rest
What is needed for optimum muscle contraction
WIDER READING - Powers 2008
physiological levels of ROS are essential for optimal force production in skeletal muscle. Nonetheless, high levels of ROS promote skeletal muscle contractile dysfunction resulting in muscle fatigue.
What are the limits of studying free radicals in vivo
WIDER READING - Powers 2008
Cant measure the production rate of free radicals
Very reactive so not around for long
Possible that the high oxygen environments in vitro are not representitive of vitro phenotypes
What is one new method that may be used in the future for ROS identificaiton
WIDER READING - Belousov VV 2006
HyPer - genetically encoded probe that can be transfected into mammalian cells and in which yellow fluorescent protein is inserted into the regulatory domain of the prokaryotic hydrogen peroxide sensing protein OxyR
What chemical is said to increase muscle strength by eliminating fatigue
WIDER READING - Mason et al 2016
N-acetylcysteine - >70mg/kg body mass
Dangerous in high doses - drowsiness
What does superoxide become downstream
Hydrogen peroxide
How does fentons reaction affect calcium sensitivity (acutely)
WIDER READING - Murphy 2008
H2O2, through the Fenton reaction, interacts with Fe2+ on myoglobin to produce the highly reactive OH•
This decreases myofibrillar calcium sensitivty and therefore contraction in muscles
What does a reduction in ROS or RNS do during fatigue and why
EXTRA READING
reducing ROS/RNS during fatigue would impair rather than improve performance.
This may be because other types of ROS/RNO dominate over H2O2
What do vitamin C and E supplements do for endurance training Paulsen et al 2014
Hamper endurance training in humans and rodents
What is malonaldehyde
Malondialdehyde (MDA) is formed during oxidative degeneration as a product of free oxygen radicals, which is accepted as an indicator of lipid peroxidation.
What role does ROS in low levels have on insulin resistance
WIDER READING – Brauer 1992
Can enhance insulin action
