Reactive oxygen species - Apoptosis
9 important questions on Reactive oxygen species - Apoptosis
What is an inhibitor of apoptosis? What interacts with this?
Inhibition by SMAC/DIABOLO => activated by the mitochondria.
What is the intrinsic apoptotic pathway? (7)
- It starts with DNA damage.
- activation p53.
- Bax/Bak oligomerize => form pores in the outer mitochondrial membrane.
BAK = Bcl-2 homologous killer
- This results in the release of cytochrome C.
- cytochrome c binds to APAF-1(apoptotic protease activating factor)
- Procaspase-9 cleaved into caspase-9.
- This activates caspase-3 and 7
- This results in apoptis
What is the role of BID (Bcl2-interacting domain)?
It activates => BAX/BAK
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What is the extrinsic pathway (4)
- Immune related ligands (FasL, TNF-α, TRAIL, TL1A) bind to the fas death receptor.
- Activation of pro-caspase 8 & 10 via FADD (fass associated protein with death domain).
- Activation of caspase 3,6,7
- Apoptosis
What is a biomarker for cytotoxicity? (maar is ook functioneel)?
In many inflammatory diseases such as hepatitis, rheumatoid arthritis and meningitis, plasma measurements have shown a large increase of various cytokines; indirect estimate of the progression of the disease in response to therapy
What is the synergy between TNF-alpha and diclofenac?
- Diclofenac => creates stress in the cel.
- TNF-alpha alone not strong enough => but with the stress strong enough to create a complete stress cascade
- Cell dies earlier.
What are the three main biochemical changes observed in apoptosis?
2.Breakdown of DNA and protein
3.Membrane changes and recognition by phagocytic cells.
What is a necrosis marker?
What are cellular changes during apoptosis?
- Endoplasmatic reticulum fragmentation
- Translational shut down
- Golgi fragmentation
- Actin bundle contraction to form a apoptotic bleb
- Changes in the membrane: PS (phosphatidylserine) flip
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