Apoptosis
Terms
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- Necrosis
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- cell “murderâ€
- cell swells and bursts
- PM integrity lost
- No alteration of nucleus
- Cause: toxic stimulus or acute injury
- Consequence: Tissue damage, inflammatory response induction - Apoptosis
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cell “suicideâ€
induction of cells intrinsic suicide program in irreparable cells
1. chromatin compaction and segregation
2. condensation of cytoplasm
3. nuclear fragmentation
4. blebbing
5. cell fragmentation
6. phagocytosed, no inflammation - Apoptosis vs. Necrosis
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No leakage of cell contents
No inflammation
Not perceptible to organism - Functions of Apoptosis
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Delete unwanted structures
Sculpt specific tissues
Control cell numbers (nerve cells)
Elimination of abnormal, nonfunctional or dangerous cells - Too Little Cell death
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Cancer
Autoimmune disorders
Viral infections - Too Much Cell Death
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-Neurodegenerative d/o (alzheimers; parkinsons)
-Osteoporosis
-AIDS
-Spinal cord injuries
-Stroke
-Heart Attack - Functions of Apoptosis in Adulthood
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-Control cell numbers
-Eliminate damaged, mutated, or infected
-Reversible development of particular organs (birdsong) - Triggers of Apoptosis
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-Withdrawal of positive signals (for continued survival)
-Receipt of negative signal (signal to die)
-Interplay of both + and – signals - Factors that Drive Apoptosis
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-Bcl-2 Family members which regulate pro or anti apoptotis
-Adapters that convert pro-caspases into active proteases
-Caspases: executioner proteases - Caspases
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-Cysteine proteases that cleave C-side of Aspartate
-Synthesized as pro-enzymes that are converted to active form
-Specific intracellular targets, cleavage of which leads to apoptosis - Activation of caspase
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-Extracellular via Fas protein and Killer T cell
-Intracellular via Cytochrome C from mitrochondria - Triggers of Ctyochrome C release from Mitochondria
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-Withdrawal of survival factors
-Receptor ligand interactions (TNF)
-Cell damage
-Aging, mitochondrial DNA damage - Regulation of Cytochrome C release
- BCL-2 Family
- “Eat me†signal on apoptotic cell
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=Phosphatidyl Serine on outer leaflet of PM
(normally only on inside)
-Phagocytotic Cells have PS receptor