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31 Cards in this Set
- Front
- Back
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Stimuli for Necrosis
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Severe and acute injury
Hypoxia, lack of glucose, toxins ALWAYS pathological |
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Stimuli for Apoptosis
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Physiological and pathologic factors - Activated by the body
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Histological Signs of Necrosis
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Cytoplasmic and mithochondrial swelling
Destruction of plasma membrane Leakage of cellular content Production of immune response |
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Histological Sings of Apoptosis
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Single cell death
Chromatin condensation Apoptotic bodies Cell shrinkage, no leakage INTACT plasma membrane -->no immune response No mitochondrial swelling |
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DNA Breakdown in Necrosis
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Random degradation, results in continuum smear in electophoresis
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DNA breakdown in Apoptosis
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Internucleosomal, very specific cuts
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Mechanism of initiation for Necrosis
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ATP depletion
Membrane Injury Free radical damage |
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Mechanism of initiation for Apoptosis
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Gene Activation
Involvement of endonucleases and proteases |
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Tissue Reaction - Necrosis
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Immune Response--> Inflammation
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Tissue Reaction - Apoptosis
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No Inflammation
Phagocytosis of apoptotic bodies |
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Stimuli for Necrosis
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Severe and acute injury
Hypoxia, lack of glucose, toxins ALWAYS pathological |
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Stimuli for Apoptosis
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Physiological and pathologic factors - Activated by the body
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Histological Signs of Necrosis
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Cytoplasmic and mithochondrial swelling
Destruction of plasma membrane Leakage of cellular content Production of immune response |
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Histological Sings of Apoptosis
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Single cell death
Chromatin condensation Apoptotic bodies Cell shrinkage, no leakage INTACT plasma membrane -->no immune response No mitochondrial swelling |
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DNA Breakdown in Necrosis
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Random degradation, results in continuum smear in electophoresis
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Ced-3
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Required for apoptosis
Pro-apoptosis Main enzymatic killer Homologous to Caspase-9 |
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Ced-4
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Required for apoptosis
Pro-apoptosis Adaptor protein required for activation of Ced-3 Homologous to Apaf-1 |
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Ced-9
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Negative regulator of apoptosis
Anti-apoptosis Inhibits Ced-4's ability to activate Ced-3 |
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Actions of Ced-3
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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 |
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Bcl-2
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Prevents leakage of cytochrome from mitochondria
Anti-apoptotic Inhibits caspase activation |
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Bad, Bax, Bak, Bid
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Comprise the Bcl-2 family
Pro-apoptotic Dimerize with Bcl-2 and inhibit it's fuction Activate caspases |
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Mitochondria Pathway
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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 |
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Receptor Pathway
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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.
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Cell Survival Signaling
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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. |
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Mechanism of Apoptosis
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Signaling
Control and Integration Execution Removal of dead cells |
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Signaling in Apoptosis
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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) |
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Control & Integration
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Signal transduction pathways connect original external death signal to the final execution program
Caspase-9 and Apaf-1 Adaptor Proteins PI 3-Kinase Pathway |
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Execution
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Protein cleavage by caspases
DNA breakdown |
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Removal of dead cells
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Markers on cell surface
Flipping of phosphatidiylserine from the cytoplasmic membrane to the extracellular surface No leakage of cytoplasmic content-->no immune response |
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Role of Apoptosis in Cancer
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Apoptosis is inhibited due
mutation of p53 protein which prevents inhibition of BAX |
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Role of Apoptosis in HIV/AIDS
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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) |
