Unit 3 - Lecture 23/24 Flashcards
Reactive Oxygen Species (ROS) are/are not naturally produced in the body.
Are
What is oxidative stress?
It is a balance between and pro-oxidants and anti-oxidants.
Tissue response to ROS:

Markers of Reactive Oxygen Species (ROS)
- Protein Oxidation
- DNA Damage
- Lipid Peroxidation
Markers of Reactive Oxygen Species (ROS)
- Basal
- Signaling
- Damage
Effects on Muscle Contraction from Reactive Oxygen Species (ROS):
- At rest, there is not much effect on muscle contraction at basal levels.
- As for exercise increases (volume/intensity/frequency), there is an increase in signaling.
- As exercise increases, potential overtraining has a damaging effect on muscle contraction.
What does the tissue responses to reactive oxygen species (ROS) suggest?
- ROS, in balance, plays an important role in adaptation.
- Exercise (muscle contraction) can help increase ROS for adaptation and increase antioxidant capacity.
Exercise attenuates:
- DNA Damage
- Lipid Peroxidation
- Protein Oxidation
How does exercise increase ROS, yet protect against ROS-induced mechanisms of disease?
There are four factors affecting the magnitude of exercise ROS onset:
- Age
- Older individuals have a greater magnitude of a response than younger individuals.
- Training Status
- The higher trained you are, the lower magnitude of the oxidative stress response.
- Dietary Intake
- Fat, especially saturated fat, produces the most oxidative stress of any macronutrient.
- Degree of Antioxidants Present
- Individuals who have more antioxidants than others are more protected.
Practically, sedentary older adults with poor diets favor oxidative stress onset.
How do we prevent excess ROS?
- Exercise
- ROS is critical for muscle homeostasis.
- ROS increases cell antioxidants.
- ROS increases cell cytoprotective enzymes that prevent damage.
What is nuclear factor-kB (NF-kB)?
- NF-kB is a transcriptional factor that regulates multiple aspects of innate and adaptive immune functions and serves as a pivotal mediator of inflammatory responses.
- NF-kB induces the expression of various pro-inflammatory genes, including those encoding cytokines and chemokines, and also participates in inflammasome regulation.
- NF-kB plays a critical role in regulating the survival, activation, and differentiation of innate immune cells and inflammatory T cells.
- Deregulated NF-kB activation contributes to pathogenic processes of various inflammatory diseases.
Reactive Oxygen Species (ROS) stimulates the activation of NF-kB.

- In the cytosol, increased levels of ROS can phosphorylate IkB proteins.
- Phosphorylated IkB initiates ubiquitination and subsequent IkB degradation via the proteasome.
- Degradation of IkB proteins removes the inhibition and releases NF-kB complexes so that nuclear translocation will occur.
- NF-kB is a transcriptional factor that regulates pro-inflammatory genes. It also has a role in cell stress and apoptosis.
- Oxidative stress can promote NF-kB.
NF-kB also regulates __________.
- Antioxidants
- There are specific enzymes that are key to this process.
- SOD = Superoxide Dismutase
- NOS = Nitric Oxide Synthase
- eNOS = Endothelial Nitric Oxide Dismutase
- Found in endothelial cells.
- iNOS = Inducible Nitric Oxide Dismutase
- Found in myocytes.
- eNOS = Endothelial Nitric Oxide Dismutase
- There are specific enzymes that are key to this process.
- Both SOD and NOS have specific promoter regions for NF-kB.
What happens during intermittent NF-kB?
- Adaptation
- Improve fuel provisions and increase antioxidants.
- Tissue regeneration.
- Benefit physiology.
What happens to chronic activation of NF-kB?
- Exhaustion
- Metabolic and oxidative perturbations.
- Tissue degradation
- Pathology
How does fuel provisions/selection fit here?
- ROS stimulates AMPK, leading to PGC1-alpha stimulation, which increases mitochondrial biogenesis.
- ROS, through a series of steps, can support greater oxidative capacity.
- It can promote increased mitochondria, which can favor fuels like fat or carbohydrate.
- Ultimately, ROS contributes to metabolic adaptations.
- AMPK has promoter regions that ROS can activate.
- Of interest, PGC1-alpha has NF-kB regions.
- NF-kB can stimulate PGC1-alpha.
- Mitochondria can be stimulated through inflammatory pathways.
- NF-kB can stimulate PGC1-alpha.
What do you think happens with antioxidant supplementation and exercise?
- Blunted adaptation to exercise (Riston, PNAS, 2008).
- Outcomes:
- Insulin Sensitivity, PGC1-alpha, Adiponectin
- Control, Vitamin C/Vitamin E
- Outcomes:
- Other data:
- SOD + NOS are blunted with supplementation.
- Flow-mediated dilation (FMD) has been reported to be blunted.
- Some evidence supports no effect on VO2max and GLUT4.
- Blunting one aspect doesn’t mean that you are blunting every response.
- Diet is not rigorously controlled in these studies.

Hormesis (54:19)
- We have seemingly dose-response systems in place with supplementation and exercise.
- Adequate stimuli = “Good Effect”
- Too many stimuli = “Bad Effect”
- Minimal effective dose.

Fatigue
- Exercise can produce oxidative stress that yields molecules like hydrogen peroxide.
- Hydrogen peroxide inhibits myosin heavy chains.
- Inhibited myosin heavy chains impair muscle contraction.
- Hydrogen peroxide inhibits myosin heavy chains.

Pharmacology in regards to antioxidants and hormesis.
What happens when we combine exercise and Metformin?
Does Drug + Exercise = 1+1 = 2?
- Exercise increases AMPK.
- Metformin increases AMPK.
- Studies indicate that drugs and exercise are not compounding.
- This is indicative of insulin sensitivity and muscle AMPK activity.
- Studies indicate that drugs and exercise are not compounding.
Metformin is believed to inhibit complex I in the electron transport chain on the inner membrane of the mitochondria.
People on Metform had blunted responses in exercise fat oxidation and VO2peak.
There is a wide range of diseases that is associated with oxidative stress.
- Diabetes
- Alcohol-induced Liver Disease
- Mitochondrial DNA disorders
- Aging
- Etc…
Can you reduce oxidative stress?
- There are a lot of opportunities from our foods to mitigate oxidative stress in the body.
- Fruits and Vegetables (Blueberries, Pomegranate
- Teas (Green Tea)
- Wine (Resveratrol)
- Cacao
Free Radicals
A molecule that contains 1 or more unpaired electrons and is capable of independent existence.
Reactive Oxygen Species (ROS)
Refers to both oxygen-centered free radicals and non-radical derivatives of oxygen (H2O2).





