Apoptosis Flashcards
What happens to nucleus?
Nucleus collapses, chromatin is cleaved and condensed
What happens to cytoplasm?
1/3 volume loss in seconds, cytoskeletal changes causes cell to tear apart
What happens to plasma membrane?
Scrablase flips phosphatidyl serine to extracellular side where it is recognized by phagocytes
Apoptosis vs Necrosis
Necrosis: mitochondrial swelling, ATP starving, Ion gradient failure, cell lysis, inflammatory response.
Apoptosis: controlled death through caspases, chromatin fragmentation, phagocyte signaling, cytosol volume loss, no lysis, no inflammatory response.
Tissues with most apoptosis
Thymus: development of thymocytes
Epithelium: rapid turn over of highly active cells
Tissues with least apoptosis
Neurons: low division rate, cells must be maintained
Caspase
Intracellular proteases that produce apoptotic phenotype.
Two types: effector and executioner
Caspase 8
effector caspase in extrinsic pathway, activated by FADD. Activates caspase 3
Caspase 9
effector caspase in intrinsic pathway, activated by Apaf-1. Activates caspase 3
Caspase 3
Executioner caspse activated by caspases 8 and9 9
Intrinsic Pathway
Bcl2 usually stops CyC release from mitochondria. Apoptotic signaling from PUMA/BIM causes Bcl2 to dissociate from mito and allow Bax to mediate Cyc release via membrane permeation.
Cyc activates Apaf-1 which activates caspase 9 which activates caspase 3
Extrinsic Pathway
Killer T Cell recognizes antigen on MHC, Fas-ligand or CD95 ligand binds Fas or CD95 on cell. FADD is recruited which activates Caspase 8 which activates caspase 3.
Phagocytosis of apoptotic vs necrotic cells
Apoptosis attracts phagocytes through flipped phosphatidylserine, there is no lysis and local inflammatory response. Anti-inflammatory TGFb is released.
Necrosis causes lysis and local inflammatory response.
Apoptosis in Tumor Formation
Cancers tend to reduce apoptosis through oncogene and tumor suppressor mutations.
