Robbins chapter 2 Flashcards
Which caspases are activated in the intrinsic apoptosis pathway and the extrinsic one and the pyroptose
caspase-9
caspase 8, caspase 10
caspase 1
Name 2 things that the caspases activated in the execution phase do
- cleavage of an inhibitor of DNase. Then DNase is enzymatically active and DNA start to degrade
- Proteolyzation of the structural components of the nucler matrix
what is efferocytosis
phagocytosis of apoptotic cells
which apoptotic pathway is used o remove self reactive T lymphocytes?
extrinsic
Example of physiologic necroptose
growth plate
What does P53 does in case of dammage to DNA (2 options)
- Stops cells in G1 and actiates DNA repair mechanisms
- Triggers apoptosis if DNA can’t be repaired
Note that a lot of cancers are linked to problems with P53
What is the role of t-PAS (theme: coagulation)?
a plasminogen activator (plasminogen->plasmin-> fibrinolysis
Résume l’hémostase primaire, et secondaire
primaire: platelet plug
secondaire: facteur tissulaire exposé-> cascade de coagulation-> génération de thrombine-> cleaves fibrinogen in fibrin
COagulation: PT et PTT, lequel est la voie extrinseque et lequel intrinseque
PT: extrinseque
PTT: intrinseque
hémoarthrose, hémorragies dans muscle: typique plus de pb hémostase primire ou secondaire?
secondaire
Les thrombus veineux sont dngereux pour quelle raison? et les thrombus dans les artères?
- veine: embolistion dans les poumons
- artère: occlusion d’une artère importante: ex: artere coronaire ou artère cérébrale
Quel complexe cyclin-CDK fait la régulation des check points de G2-M?
cyclin B-CDK1
True or false: mitochondria normally produces ROS
True
which is the most reactive oxygen derived free radical?
OH
Why does ferritin, lactoferrin, transferrin and ceruloplasmin help in reducing free radicals?
Fe2+ and copper catalyze free radical formation
which anti free radical enzyme is present in peroxisomes?
Catalase
What is the misfolded protein response (it does 3 things)
When too many misfolded proteins in the ER-> ER stress->
1. Increase production of chaperones
2. decrease protein translation
3. proteasome action
If not sufficient-> apoptosis
Heart: Increased workload + agonists (ex: alpha adrenergic hormones, angiotensin) and growth factors cause myocardial hypertrophy via 3 effects/pathways:
production of growth hormone
activation of fetal/embryonic genes
Production of contractile proteins
For the production of melanin, the enzyme ______ catalyses the oxidation of ______ to dihydroxyphenylalanine
tyrosinase, tyrosine
Is cell injury reversible?
Yes, to a point. Cell injury means it is past the limits of adaptative response
what is dystrophic calcification?
calcium accumulated at site of necrosis
Give two example of early alteration of cells in reversible injury (can be observed visually)
Cell swelling
fatty change
Cause of cell swelling in injury of cells
lack of oxygen-> Depletion of ATP-> ATP Na K plasma membrane pump not working
What is hydropic change/vacuolar degeneration? (which organelle is afected?)
endoplasmic reticulum that is distended
Give 2 DAMPs (dammage associated molecular patterns) that triggers inflammation and cytokines
ATP and uric acid
What causes increased eosinophilia in cells with injury?
denatured proteins accumulating in cytoplasm
what are myelin figures
concentric lamellations made up of phospholipids and calcium that are derived from cell membranes (seen in réversible or irreversible injury)
Which protein is a proapoptotic enzyme when leaked from mitochondria?
Cytochrome C (mitochondrial or intrinsic pathway of apoptosis)
Name 3 antiapoptotic proteins. What are they induced by?
BCL2, BCLX, MCL1.
In membranes and in cytosol, they prevent leakage of cytochrome C.
Is induced by survival signals including growth factors
BAX and BAK are proapoptotic because they ________________ the mitochondria membrane.
BIM, BAD and BID, as well as noxa and puma are apoptosis ______________
permeabilize, initiators
Which is the initiator caspase of the mitochondrial pathway?
caspase 9
What is the apoptosome constituted of?
cytochrome C binding to APAF-1 (apoptosis activating factor 1)
Which receptors initiate the extrinsic pathway of apoptosis?
plasma membrane death receptors
True or false hypoxia can elicit inflammation?
true. Endogenous substances like cholesterol crystals and lipids as well
Does chronic inflammation always happens after acute inflammation?
No, can happen de novo
what are the 2 things that are consistants with irreversible injury
inability to reverse mitochondrial dysfunction and profound disturbance in membrane function
What is the role of BH3 only proteins in apoptosis?
antagonise BCL2 and activate BAX and BAK.
They are activated when lack of survival signals or other damage of the cell
What is the role of Smac/DIABLO
they are mitochondrial proteins that bind IAP (inhibitors of apoptosis). So the ultimate effect of Smac/DIABLO is proapoptosis
What does the protein FLIP do?
Bind procaspase 8, preventing FADD (Fas-associated death domain, in extrinsic apoptosis) from binding to it, therefore preventing apoptosis
necroptosis: give an exemple of a physiologic etiology and a pathologic etiology
groth plates, acute pancreatitis, cytomegalovirus, ishemia reperfusion, neurodegenerative disease, steatohepatitis
what is the fenton reaction?
Fe2+ (ferrous) + H2O2 - > Fe3+ (ferric) + 2OH-
copper-zinc SOD and manganese SOD: which one is in the cytoplasm/mitochondria?
Copper zinc SOD is in the sytoplasm and manganese is in the mitochondria
what does the accumulation of calcium in the mitochondria has as a consequence?
opening of the mitochondria permeability transition pore
why does the complement contributes to reperfusion injury?? What tend to deposit in ischemic tissues?
IgG
Which pathway is more important in physiologic hypertrophy? In pathologic (generic)?
physiologic hypetrophy: PI3K/AKT
pathologic hypertrophy: G protein coupled receptor-initiated pathways
