Cell survival mechanisms Flashcards
What 4 pathological processes cause stress on aerobic organisms?
- Reactive oxygen species
- DNA damaging electrophiles / carcinogens
- Inflammatory / infection - accompanied by ROS and electrophiles
- Radiation
What are the 4 cytoprotective systems of aerobic organisms?
- small molecular direct antioxidants
- housekeeping antioxidant enzymes
- DNA-damage repair systems
- Inducible cytoprotective enzymes
Examples of small molecular direct antioxidants
- glutathione
- ascorbate
- alpha-tocopherol
Types of housekeeping antioxidant enzymes
- catalase
- superoxide dismutase
What are the DNA damage repair systems?
Single strand breaks - Excision Repair - Mismatch Repair Double stranded breaks - Non-homologous end joining - Microhomology-mediated end joining - Homologous recombination
what is the pathway for inducible cytoprotective enzymes
The Keap1-Nrf2 pathway
What is Nrf2?
a transcription factor which regulates cytoprotective genes
What is the function of Keap1?
Regulates Nrf2 and acts as a sensor for oxidative and electrophilic stress
What is the function of sulforaphane?
Stop ubiquitylation of Nrf2
What does the activation of Nrf2 by sulforaphane protect against?
- streptozotocin-induced diabetic nephropathy
- diabetes induced aortic damage
- stops oxidative stress associated with diabetes induced aortic damage
- protects brain against hypoxia-ischemic injury by cytoprotective enzymes
- decrease inflammation and lesion volume after spinal cord injury
What is Keap1?
A cysteine rich protein (highly reactive cysteines)
Give the equation for the isolation and identification as sulforaphane as a potent NQO1 inducer
Glucoraphanin -(Myrosinase)[H2O in, Glucose out]-> Unstable Aglucon -[HSO4- out]-> Suforaphane
Property of glucoraphinin
Has no inducible ability
Property of sulforaphane
high biological activity
How does sulforaphane activite Nrf2?
by reacting with cysteine on Keap1
