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31 Cards in this Set

  • Front
  • Back
Stimuli for Necrosis
Severe and acute injury
Hypoxia, lack of glucose, toxins
ALWAYS pathological
Stimuli for Apoptosis
Physiological and pathologic factors - Activated by the body
Histological Signs of Necrosis
Cytoplasmic and mithochondrial swelling
Destruction of plasma membrane
Leakage of cellular content
Production of immune response
Histological Sings of Apoptosis
Single cell death
Chromatin condensation
Apoptotic bodies
Cell shrinkage, no leakage
INTACT plasma membrane -->no immune response
No mitochondrial swelling
DNA Breakdown in Necrosis
Random degradation, results in continuum smear in electophoresis
DNA breakdown in Apoptosis
Internucleosomal, very specific cuts
Mechanism of initiation for Necrosis
ATP depletion
Membrane Injury
Free radical damage
Mechanism of initiation for Apoptosis
Gene Activation
Involvement of endonucleases and proteases
Tissue Reaction - Necrosis
Immune Response--> Inflammation
Tissue Reaction - Apoptosis
No Inflammation
Phagocytosis of apoptotic bodies
Stimuli for Necrosis
Severe and acute injury
Hypoxia, lack of glucose, toxins
ALWAYS pathological
Stimuli for Apoptosis
Physiological and pathologic factors - Activated by the body
Histological Signs of Necrosis
Cytoplasmic and mithochondrial swelling
Destruction of plasma membrane
Leakage of cellular content
Production of immune response
Histological Sings of Apoptosis
Single cell death
Chromatin condensation
Apoptotic bodies
Cell shrinkage, no leakage
INTACT plasma membrane -->no immune response
No mitochondrial swelling
DNA Breakdown in Necrosis
Random degradation, results in continuum smear in electophoresis
Ced-3
Required for apoptosis
Pro-apoptosis
Main enzymatic killer
Homologous to Caspase-9
Ced-4
Required for apoptosis
Pro-apoptosis
Adaptor protein required for activation of Ced-3
Homologous to Apaf-1
Ced-9
Negative regulator of apoptosis
Anti-apoptosis
Inhibits Ced-4's ability to activate Ced-3
Actions of Ced-3
Destroys an enzyme which inhibits fragmentation of DNA
Destroys nuclear lamins leading to fragmentation of the nucleus
Destroys cytoskeletal proteins leading to membrane blebbing and cell fragmentation
Bcl-2
Prevents leakage of cytochrome from mitochondria
Anti-apoptotic
Inhibits caspase activation
Bad, Bax, Bak, Bid
Comprise the Bcl-2 family
Pro-apoptotic
Dimerize with Bcl-2 and inhibit it's fuction
Activate caspases
Mitochondria Pathway
Cell Death
Cytochrome activates Caspase-9
Apaf-1 binds to caspase-9 and promotes its activation
Caspase-9 cleaves and activates Caspase-3
Caspase-3 destroys cell
Receptor Pathway
Membrane receptors bind TNF or FasL and send a message to cytoplasm to activate Caspase-8 which cleaves and activates Bid(pro-apoptotic). Caspase-8 moves to mitochondria where it dimerizes and inhibits Bcl-2. Cytochrome C then escapes mitochondria and initiates apoptotic pathway in cell.
Cell Survival Signaling
Signaling pathways actively inhibit apoptosis
Phosphoinosital 3-kinase phosphorylates PIP2 to PIP3
Akt and PDK-1 bind PIP3 and are activated
Active Akt phosphorylates Bad in cytoplasm to P-Bad. P-Bad is recognized and degraded by proteases. No Bad means no apoptosis.
Active Akt also produces transcription factors and GSK-3 which activates other pro-life factors.
Mechanism of Apoptosis
Signaling
Control and Integration
Execution
Removal of dead cells
Signaling in Apoptosis
Variety of Signals:
Intrinsic programmed event(developmental ie. webbing b/t fingers)
Lack of growth factors
Specific rector-ligand interactions
Exposure to a toxic agent (radiation)
Control & Integration
Signal transduction pathways connect original external death signal to the final execution program
Caspase-9 and Apaf-1
Adaptor Proteins
PI 3-Kinase Pathway
Execution
Protein cleavage by caspases
DNA breakdown
Removal of dead cells
Markers on cell surface
Flipping of phosphatidiylserine from the cytoplasmic membrane to the extracellular surface
No leakage of cytoplasmic content-->no immune response
Role of Apoptosis in Cancer
Apoptosis is inhibited due
mutation of p53 protein which prevents inhibition of BAX
Role of Apoptosis in HIV/AIDS
Inhibition of apoptosis in infected cells so that HIV can use cells as incubators
Apoptosis in uninfected CD4+ T lymphocytes
Apoptosis in CD8 T lymphocytes (cells which eliminate foreign cells)
Apoptosis in brain neurons (massive cell loss)