11/12/18
Dr Daniele Bergamaschi
Apoptosis
• Meaning “dropping off”
• Happens automatically in cells at the end of their lifespan
o Vital for life and regeneration
• 50-70 billion cells per day undergo apoptosis in human adults
Development
• Major role in morphogenesis and tissue remodelling
o E.g tadpole tail removed when metamorphosis into frog
o E.g. individualism of digits
Diseases
• E.g. excessive linked to neurodegenerative diseases and organ failure after infarction or
toxic insult
• E.g. defective apoptosis involved in cancer
Necrosis vs. Apoptosis
• Necrosis is swelling of cell and organelles then a ruptured membrane with cell contents
released
• Apoptosis is:
o Cellular and nuclear shrinkage (change in shape and size)
o Disassembly into apoptic bodies
o Cell engulfment and chromatin condensation (pycnosis)
o Internucleosomal DNA fragmentation
o Mitochondrial membrane permeabilization (MMP)
o Cytochrome C moved from mitochondria to cytoplasm
o Capases cascade activation
Membrane
• Annexin V-PE conjugate deposited in membrane
• Calcium ions attracted (opens calcium channel)
• Externalisation of phosphatidylserine
Caspase Cascade
• Intracellular proteolytic cascade mediated by caspases
• Cleave target proteins
• For inflammation:
o 1 (ICE), 4, 5
• For apoptosis:
o Initiators – 2, 8, 9, 10
o Executioner – 3, 6, 7
Dr Daniele Bergamaschi
Apoptosis
• Meaning “dropping off”
• Happens automatically in cells at the end of their lifespan
o Vital for life and regeneration
• 50-70 billion cells per day undergo apoptosis in human adults
Development
• Major role in morphogenesis and tissue remodelling
o E.g tadpole tail removed when metamorphosis into frog
o E.g. individualism of digits
Diseases
• E.g. excessive linked to neurodegenerative diseases and organ failure after infarction or
toxic insult
• E.g. defective apoptosis involved in cancer
Necrosis vs. Apoptosis
• Necrosis is swelling of cell and organelles then a ruptured membrane with cell contents
released
• Apoptosis is:
o Cellular and nuclear shrinkage (change in shape and size)
o Disassembly into apoptic bodies
o Cell engulfment and chromatin condensation (pycnosis)
o Internucleosomal DNA fragmentation
o Mitochondrial membrane permeabilization (MMP)
o Cytochrome C moved from mitochondria to cytoplasm
o Capases cascade activation
Membrane
• Annexin V-PE conjugate deposited in membrane
• Calcium ions attracted (opens calcium channel)
• Externalisation of phosphatidylserine
Caspase Cascade
• Intracellular proteolytic cascade mediated by caspases
• Cleave target proteins
• For inflammation:
o 1 (ICE), 4, 5
• For apoptosis:
o Initiators – 2, 8, 9, 10
o Executioner – 3, 6, 7
