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24 Cards in this Set
- Front
- Back
What is this?
-cell murder -due to unexpected or accidental cell damage -overwhelming insults by toxins, radiation, heat, trauma, lack of oxygen |
Necrosis
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what is this?
-non-traumatic cell death, “programmed cell death”, “cell suicide” -may result from viral infections, cellular stress, DNA damage (prevention of cancer), or as part of normal development and maintenance of tissue |
Apoptosis
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is this apoptosis or necrosis?
Physiological or pathological Single cells Energy dependent Cell shrinkage Membrane integrity maintained Role for mitochondria and cytochrome C No leak of lysosomal enzymes Characteristic nuclear changes Apoptotic bodies form DNA cleavage Activation of specific proteases Regulated process Evolutionarily conserved Dead cells ingested by neighbouring cells |
apoptosis
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Is this apoptosis or necrosis?
Always pathological Sheets of cells Energy independent Cell swelling Membrane integrity lost No role for mitochondria Leak of lysosomal enzymes Nuclei lost Do not form No DNA cleavage No activation Not regulated Not conserved Dead cells ingested by neutrophils and macrophages |
necrosis
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The necrosis pathway:
-dependent on loss of membrane homeostasis, especially ... -... influx into cytosol (from intracellular stores and from ECM) --> ... is allosteric activator of many degradative enzymes -... --> cytosolic protease -... --> lysosomal protease |
Ca2+ homeostasis
Ca2+ Ca2+ calpain cathepsin |
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Necrosis:
cell ..., ... form in membrane, intracellular contents leak out into surrounding tissue, eventual cell ... |
swells
holes lysis |
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necrosis:
major ... results -cell contents leak into ECM, damaging surrounding tissue -production of ... from Arachadonic Acid produced during lipolysis of membrane phospholipids -recruitment of inflammatory mediators (... and ...) - cleans up cell debris |
inflammation
eicosanoids macrophages and neutrophils |
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Apoptosis is a natural normal process that’s found throughout ... and even through adulthood.
-Impt for processes like the development of the fingers -... hands will develop if apoptosis fails here |
embryogenesis
webbed |
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the apoptotic pathway:
non-traumatic, highly ordered process 3 phases involved: -... (external or internal signals)-when a signal is received by the cell that something is wrong -... (pro-apoptotic signals balanced against anti-apoptotic cell survival signals) -... (carried out by proteolytic enzymes called caspases, which digest the cell) |
Initiation phase
Signal integration phase Execution phase |
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which 4 players must be present for apoptosis to occur?
-... -... (releases cytochrome C) -... (protein) -... (protease that dismantles the cell) |
death receptor
mitochondrion bcl-2 protein active initiator caspases |
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caspases:
-Cysteine aspartate specific proteases -present in cell as ... (zymogen precursor that must be activated by proteolytic cleavage) -inactivate cellular ... pathways and specifically activate factors that promote ... |
procaspases
survival cell death |
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classes of caspases:
1) Initiator (activator) caspases: -generally cleave and activate ... -activate other enzymes 2)Effector (executioner) caspases: -requires formation of ... -cleave cellular proteins involved in maintaining ... -the ones that actually dismantle the cell |
procaspases
apoptosome cellular integrity |
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Death receptor pathway:
-subset of ... receptors -receptor forms a ... that binds TNF-1 or another death ligand (Fas ligand, p53, BAX) on its external domain -(BAX initiates process of apoptosis) -intracellular domain attached to cytosolic ... -activates ... caspases, which in turn activates ... caspases, which leads to the destruction of the cell |
TNF-1 (tumor necrosis factor)
trimer adaptor proteins initiator execution |
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mitochondrial integrity pathway (not directly linked to receptor itself):
-intracellular signals indicate death should occur (growth factor withdrawal, cell injury, release of certain steroids, inability to maintain low intracellular Ca2+) -pathway begins with release of ... from mitochondria (1st step) -... (one of the markers of apoptosis) binds ...(only found during cell death) and forms the ..., which in turn activates execution caspases |
cytochrome c
cytochrome c Apaf apoptosome |
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-formation of the apoptosome by ... and ...
-apoptosome specifically activates the ... |
cytochrome c
Apaf-1 execution caspase |
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the ... family are the decision making signals
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Bcl-2
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Put these into the right categories:
Categories: -protectors (anti-apoptotic): protect cell from undergoing apoptosis -killers (pro-apoptotic): trying to promote cell death -regulators: go either way. Responds to both signals 1)Bax, Bak, Bok/Mtd 2)Bcl-2, Bcl-xL, Bcl-W 3)Bad, Bid, Bim |
-Protectors: Bcl-2, Bcl-xL, Bcl-W
-Killers: Bax, Bak, Bok/Mtd -Regulators: Bad, Bid, Bim |
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Anti-apoptotic Bcl-2 members (Bcl-2, Bcl-x, Bcl-w):
-can insert into outer mitochondrial membrane to ... channel-forming pro-apoptotic factors (decreases cytochrome c release) -may prevent assembly of apoptosome complex by binding to and inactivating cytoplasmic ... |
antagonize
Apaf-1 |
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Pro-Apoptotic Bcl-2 members:
some may form ..., promoting cytochrome c release (Bax, Bak, Bok) some members called ... (regulator Bcl-2 proteins Bad, Bid, Bim) bind directly to other Bcl-2 members, either activating or inactivating them |
ion channels
BH3-only proteins |
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DNA changes in apoptotic cells:
1)... aggregation (forms a ring around nucleus) 2)... condensation 3)... fragmentation (not random. organized) -ordered DNA intranucleosomal cleavage producing a characteristic ... pattern on an agarose gel (highly specific and diagnostic of apoptosis) |
chromatin
nuclear nuclear “laddering” |
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Membrane changes in apoptotic cells:
-cell shrinking -membrane ... (protective mechanism so its enzymes don't spill out. prevents inflammation) -apoptotic bodies -membrane asymmetry -phosphatidylserine (PS) flips from ... to ... membrane = signal to other cells saying "i'm going through apoptosis!!! |
blebbing
inner outer |
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when ... is exposed on the outer leaflet of the membrane, it's a signal to the other cells that that cell is undergoing apoptosis
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phosphatidylserine
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Inflammation isn't assoicated with apoptosis because:
-no ... of lysosomal enzymes or cellular contents into surrounding tissue -removal of apoptotic bodies does not elicit an ... response from macrophages/neutrophils -... affected, not ... of cells |
leakage
inflammatory individual cells large groups |
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importance of apoptosis in disease:
lack of apoptosis when it should be occuring -... -... apoptosis occuring when it should not -... diseases, like Alzheimer's and Huntingtons -myocardial infarction -stroke |
autoimmunity
cancer neurodegenerative |