Cell Injury, Apoptosis, Necrosis Flashcards

Question

causes of ATP depletion?

Answer 1

hypoxia, chemical agents (toxins), reduced nutrients, mitochondrial damage

Answer 2

1. loss of Na/K ATPase 2. altered metabolism 3. detachment of ribosomes

Answer 3

increased efflux of K via leak channels, increased Ca, H2O and Na into the cell -- leading to ER swelling, cellular swelling and loss of microvilli

Answer 4

metabolism changes to anaerobic metabolism, leading to decreased glycogen, increased lactic acid, decrease in pH and clumping of nuclear chromatin (no transcription, no making proteins)

Answer 5

decrease in protein synthesis, leading to lipid deposition and irreversible damage to mitochondria and lysosomal membranes

Answer 6

an increase in cytosolic Ca, depletion of oxygen, and increase in ROS

Answer 7

forms mitochondrial permeability transition pore, that 1. creates the loss of membrane potential, oxidative phosphorylation fails due to loss of potential, and ATP is depleted and 2. allows leakage of apoptosis-activating proteins into cytoplasm, leading to activation of apoptosis

Answer 8

activation of enzymes such as phospholipase C (membrane damage), proteases (membrane damage), and endonucleases (nuclear damage), and caspases (to cause apoptosis)

Answer 9

free radicals with unpaired electron, extremely reactive and unstable

Answer 10

1. redox reactions 2. absorption of radiant energy 3. inflammation 4. enzymatic metabolism of exogenous chemicals or drugs 5. transition metals, 6. NO

Answer 11

1. lipid peroxidation in membranes (disrupts cell membranes) 2. oxidative modification of proteins (loss of enzymatic activity and abnormal folding) 3. lesions in the DNA (due to oxidation, mutations and breaks occur)

Answer 12

1. ROS 2. decreased phospholipid synthesis 3. increased phospholipid breakdown 4. cytoskeletal abnormalities

Answer 13

1. mitochondrial membrane damage (pore stops membrane potential, apoptosis-activating proteins) 2. plasma membrane damage (loss of osmotic balance and loss of cellular contents) 3. injury to lysosomal membranes (leakage of enzymes into cytoplasm leading to digestions of proteins, RNA, DNA, glycogen)

Answer 14

1. cellular swelling 2. plasma membrane alterations (blebbing) 3. mitochondrial changes (swelling, amorphous densities) 4. dilation of ER 5. minor nuclear alterations

Answer 15

1. electric shock 2. poison 3. physical injury 4. lack of oxygen

Answer 16

1. DNA damage 2. normal development 3. cell turnover

Answer 17

passive and pathological process induced by acute injury or disease - cells undergo apoptosis at the same time

Answer 18

1. denaturation of intracellular proteins and enzymatic digestion of injured cell (lysosome contents are released) 2. plasma membrane is compromised (water rushes in and cell lyses) 3. formation of myelin figures

Answer 19

large, whorled damaged phospholipids in the cytoplasm that are derived from damaged cell membranes

Answer 20

necrosis elicits inflammatory response, swells, and plasma membrane is damaged, and apoptosis is tightly controlled, cell shrinks, and plasma membrane is intact

Answer 21

1. no cell swelling due to plasma membrane staying intact 2. activation of self-degrading enzymes 3. shrinkage of cell 4. formation of apoptotic bodies 5. phagocytosed without inducing inflammatory response

Answer 22

1. microvilli contract, intercellular junctions break, chromatin condenses 2. cell shrinks, chromatin condenses around nuclear periphery 3. cell blebs violently, chromatin condensation continues 4. cell fragments into membrane-enclosed apoptotic bodies 5. apoptotic bodies phagocytosed by neighboring cells and roving macrophages

Answer 23

1. trauma 2. cells and organelles swell, chromatin condenses, membrane compromised and fluid rushes in 3. dissolution of cellular structures 4. cell lysis, invasion of phagocytic cells, inflammation

Answer 24

1. dna damage 2. misfolded proteins 3. infections

Answer 25

1. forms digits during embryogenesis 2. establishment of neuronal connections 3. lymphocyte maturation in thymus

Answer 26

cysteine proteases, containing a cysteine in the active site, which cleaves after the aspartic acid residues in substrate without apoptotic signal, are held inactivated called procaspase (prodomain must be cleaved)

Answer 27

1. activation of caspase (prodomain cleaved off procaspase) 2. dna and protein are broken down (DNA fragmented and cleavage between nucleosomal subunits) 3. membrane alteration (promotes recognition by phagocytes)

Answer 28

once procaspase is cleaved, active caspase results in amplification cascade that activates many molecules of the down stream caspase

Answer 29

first type of caspase activated, cleaves and activates executioner caspases CASPASE 2,8,9,10

Answer 30

activated by initiator caspases, activate protease and nuclease downstream CASPASE 3,6,7

Answer 31

phosphatidylserine (PS) is only found in the inner leaflet of the PM in healthy cells, in apoptotic cells PS flips to outer leaflet and the exposure services as ligand for PS receptor on surface of phagocytic cells

Answer 32

internal damage or physiologically normal elimination of cells - deprivation of nutrients, DNA damage, misfolded proteins

Answer 33

external signal initiation

Answer 34

Bcl family of proteins

Answer 35

``` BH3only: Bim, Bid, Bad Channel forming (associated with mitochondrial membrane): Bax, Bak ```

Answer 36

Bcl-2, Bcl-X, Mcl-1

Answer 37

increase in mitochondrial permeability and repease of pro-apoptotic proteins

Answer 38

transmembrane proteins located in outer mitochondrial membrane, the oligomerize to form pores in the mitochondrial membrane when signaled by apoptotic signaling

Answer 39

pore is formed in the outer mitochondrial membrane, allowing release of intermembrane sequestered proteins, including cytochrome C

Answer 40

sequestered intermembrane protein that is directly responsible for initiating apoptotic signaling cascade - once cytochrome C leaves, the cell dies

Answer 41

anti-apoptotic proteins Bcl-X, Bcl-2, and Mcl-1 produced, and bind to Bax and Bak to prevent oligomerization, maintains mitochondrial membrane integrity and prevents cytochrome C from exiting the mitochondrial intermembrane space

Answer 42

BH3 only proteins Bim, Bad, Bid inhibit the anti-apoptotic proteins (Mcl-1, Bcl-2, and Bcl-X), and Bax and Bak are allowed to oligomerize and create channels in the mitochondrial outer membrane, cytochrome C is released, cell dies

Answer 43

a large complex created by the cytochrome C that combined with adaptor proteins Apaf-1

Answer 44

recruits procaspase-9, which is cleaved to produce caspase-9, and caspase-9 activates executioner caspases (initator-->executioner-->proteases, nucleases)

Answer 45

the death receptor pathway: Fas signaling, FasL binds to FasR, when bound FasR containing cell dies

Answer 46

1. FasL binds to FasR 2. 3 FasR molecules cluster and bind the adaptor protein FADD (Fas-Associated Death Domain) through their intracellular tails 3. FADD recruits procaspase-8 molecules 4. FADD and procaspase-8 form complex alled Death-Inducing Signaling Complex (DISC) 5. procaspase-8 cleaves each other, making caspase-8 6. caspase-8 cleaves procaspases 3,6,7 to produce active executioner caspases 3,6,7

Answer 47

degrade nuclear laminins and activate DNAses that cleave genomic dna between adjacent nucelosome coils

Answer 48

fragments of DNA that are mulitples of 180bp in length - creates a laddering pattern unique to cells undergoing apoptosis

Answer 49

intrinsic pathway requires mitochondrial involvement, but activation of extrinsic pathway could lead to activation of intrinsic pathway, resulting in amplification of cellular response