Term | Definition |
apoptosis | programmed cell death, result in safe removal of cellular debris |
morphology | 1. membrane blebbing
2. loss of membrane asymmetry and attachment
3. cell shrinkage and nuclear fragmentation
4. chromatin condensation and chromosomal DNA fragmentation |
process | 1. apoptosis begins, condensation of chromosome
2. nucleus fragments, Dna is digested (laddering), cytoplasm fragments
3. apoptotic bodies are ingested by phagocytic cells |
role in normal physiology | development and metamorphosis
adaptive immune response |
role in disease | control of cell growth and proliferation
removes damage cell
activate killer cells |
excessive apo. | stroke, neurodegeneration leading to alzheimer and parkinson |
defective apo. | neoplasie, autoimmune syndromes |
Detection with ANNEXIN V | late stage; plasma membrane is compromised and nucleic acid dyes are allowed to entrance the cell and bind with DNA- marker for apoptosis |
caspases | central component for apo. -> cleavage of proteins. detection by immunoblotting tech.using caspase specific antibody or a dye. |
intrinsic pathway | triggered by non-receptor stimuli
internal damage;bcl2 inhibition by bac; making holes in MOMP &cytochrome c leakage.
cyto-c-Apaf1 complex-apoptosome;activate caspase 9,cleaves and activates 3&7 leading to digestion os structural protein&dna |
bcl2 | on the membrane of a healthy cell, inhibits apoptosis |
caspases | caspase cascade activated by proteolytic cleavage of precursor
DED and CARD domain
executioner caspases |
DED domain | death effector domain - regulate cellular signalling pathways |
CARD domain | activation and recruitment of caspases |
executioner caspases | 6,3,7 |
apoptosis inducing factor AIF | does not use caspases, located at intermembrane space of mitochondria, one signal ; released from mito. migrate to nuclus and binds to DNA where it triggers its destruction |
extrinsic pathway | external signal join with death receptor (FASL or TNF). signal transmitted to cytoplasm activating caspase 8 that initiates the cascade of caspases activation. phagocytosis |
proteolysis | hydrolytic breakdown of proteins into simpler substance |
pro- apoptotic | enhance apoptosis
BAX, BID, BAD, BIM |
anti apoptotic | inhibits apoptosis
Bcl, BCL-XL |
in cancer | increased expression of BCL2 so it stops the apoptosis of proliferating cells |