Cell Death

Question 1

Apoptosis Hallmarks

Answer 1

Membrane budding
Cell shrinkage, organellar reduction mito leakage
Chromatin condensation
DNA cleavage
Fragmentation of the cell into apoptotic bodies

Question 2

Steps of necrosis

Answer 2

Mito ATP production stops
ATP-driven ion pumps stops
Ions accumulate in the cell
Water seep into cell
Cell swells
Glycolysis continue for a while
PH decreases
Organelles swell
Calcium concentration increase
Calcium activates enzymes
Protein denaturation
Cell membrane damage
Cell dies

Question 3

Importance of apoptosis

Answer 3

Normal cell turn over
Tissue homeostasis
Induction and maintenance of immune tolerance
Development of the NS
Endocrine dependent tissue atrophy
Elimination of activated, damage and abnormal cells

Question 4

Too little apoptosis causes?

Answer 4

Cancer
Autoimmune diseases

Question 5

Too much apoptosis causes?

Answer 5

Stroke damage
Alzheimer’s

Question 6

Morphological features of necrosis

Answer 6

Loss of membrane integrity
Begins with swelling of cytoplasm and mito
Ends with total cell lysis
No vesicle formation, complete lysis
Disintegration of organelles

Question 7

Morphological features of apoptosis

Answer 7

Membrane blebbing, but no loss of integrity
Aggregation of chromatin at the nuclear membrane
Begins with shrinking of cytoplasm and condensation of nucleus
Ends with fragmentation of cell into smaller bodies
Formation of membrane bound vesicles
Mito become leaky due to pore formation

Question 8

Biochemical features of necrosis

Answer 8

Loss of regulation of ion homeostasis
No energy
Random digestion of DNA
Postlytic DNA fragmentation

Question 9

Biochemical features of apoptosis

Answer 9

Tightly regulated process involving activation and enzymatic steps
Eagerly dependent
Non-random mono- and oligonucleosomal length fragmentation of DNA
Prelytic DNA fragmentation
Release of cyt c, AIF
Activation of caspase cascades
Alterations in membrane asymmetry

Question 10

Physiological factors of necrosis

Answer 10

Affects groups of cells
Evoked by non-physiological disturbances
Phagocytosis by macrophages
Inflammatory

Question 11

Physiological features of apoptosis

Answer 11

Affects individual cells
Induced by physiological stimuli
Phagocytosis by adjacent cells or macrophages
No inflammatory

Question 12

Why is apoptosis better than necrosis

Answer 12

Because necrosis causes inflammation and apoptosis not

Question 13

What makes cell decide to commit suicide

Answer 13

Withdrawal of living signals= growth factors for neurons, IL-2
Receipt of death signals= increased level of oxidants within cell, damage to DNA by oxidants, death activators : TNF-a,b ,FasL

Question 14

Phases of apoptosis

Answer 14

Induction = reversible
Effector =irreversible
Degradation= irreversible

Question 15

What are the roles of Calcium in the phases of apoptosis

Answer 15

Induction phase = second messenger
Effector phase = Bcl-2 cofactor
Degradation phase= protease and nuclease activator

Question 16

Categorization of caspases

Answer 16

Signaling/ Initiator = 2,8,9,10
Effector/ Executioner = 3,6,7
Inflammatory= 1,4,5

Question 17

What is the main role of caspases

Answer 17

Cleavage of restricted set of proteins

Question 18

Caspase targets

Answer 18

Cytoskeletal proteins
Regulators of DNA repair
RNA splicing protein
NEVER NUCLEUS

Question 19

What are the groups of Bcl-2 family

Answer 19

1= Bcl-2 and Bcl-xl anti-apoptotic, outer surface of mito and ER
2= Bax and Bak pro-apoptotic
3= Bid and Bik pro-apoptotic

Question 20

Why Bcl-2 and Bcl-xl is anti-apoptotic

Answer 20

Bc they have a BH4 domain which is a surviving domain

Question 21

How do Bcl-2 family control cell death

Answer 21

They block each other’s next move
Regulate the release of cyt c
Inhibition of calcium effluent from ER
Inhibit ROS formation

Question 22

Role of mito in apoptosis

Answer 22

Disruption of electron transport
Release proapoptotic proteins
Free radicles
PERMEABILITY TRANSITION RELEASE CYTC C

Question 23

How does mito release cytc c

Answer 23

Normally on the surface of mito membrane there are Bcl-2 which inhibts the Bak.
When death singnal comes Bcl-2 is inhibited and opens gates on the membrane of the mito
With this inhibition Bak is no longer inhibited which regulates the release of the cytc c

Question 24

What is the role of Apaf-1

Answer 24

With the cytc c it activates inactive caspase 9

Question 25

Death receptors

Answer 25

(CD95)FAS,TNF-R

Question 26

Extrinsic pathway of apoptosis

Answer 26

Death signals — death receptors— initial caspase 8– effector caspase 3 — death

Question 27

Intrinsic pathway of apoptosis

Answer 27

DNA damage and p53– mito—cytc c—initiation caspase 9–effector caspase 3–death

Question 28

Signals to death

Answer 28

Intrinsic = p53
Extrinsic= FAS,TNFR,DR2,TRAIL receptors

Question 29

P53

Answer 29

Located on chromosome 17
Normally levels are low
Normally it stops cell at G1 or interphase
Induction of apoptosis in DNA damage
Any disruption to the regulation of p53 will result in the possible formation of tumors
Activated by DNA damage

Question 30

What are the possibilities when p53 increases

Answer 30

1= cell cycle arrest— DNA repair— cell lives
2= cell cycle arrest— irreparable damage — apoptosis

Question 31

How does neighboring cells understand the cell needs to be engulfed

Answer 31

Normally phosphatidylserine is in the inner side of plasma membrane
But it fliğps out during apoptotic steps
Neighboring cells understand these as a eat me signal

Question 32

Apoptosis in neurodegeneration

Answer 32

Parkinson’s
Alzheimer’s
Huntingtons

Question 33

Apoptosis in aging

Answer 33

In both too much and too little apoptosis causes aging