Brainscape's Knowledge GenomeTM


Top Flashcards (Certified)
All Flashcards

Cell Biology (BY1CB1) > Week 10 (Apoptosis) > Flashcards

Week 10 (Apoptosis) Flashcards

(63 cards)

Start Studying
1
Q

What is Apoptosis?

A

Cell death
–in normal physiology (death can be physiological)
–In disease

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is the function of apoptosis?

A
  • Removes damaged, unwanted or diseased cells

* Programmed cell death = Ordered cell deletion

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

C. elegans

A

–powerful model system
–191 predictable deaths in development
–highly tractable system
–study regulation, activation and execution of apoptosis
•Model systems have underpinned current knowledge

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What is Apoptosis is crucial for?

A

–development
–maintenance
–control

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Cell Population Control

A

Proliferation+
Differentiation -/+
Cell Death -

There is no net change in number of cells

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

Examples of diseases caused by Overactive Apoptosis?

A 
More cells dying than proliferating
–Neurodegeneration
–Immunodeficiency
–Stroke
–Coronary Heart Disease
–Transplant Rejection
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Examples of diseases caused by Underactive Apoptosis

A

More cells proliferating than dying
–Cancer
–Autoimmune & Inflammatory conditions
–(e.g. SLE and rheumatoid arthritis)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

The Importance of Apoptosis

A

Life-death imbalance can be desirable (physiological)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Why can Underactive Apoptosis be desirable?

A

–Allows cell accumulation (e.g. accumulation of cells during an immune response)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What why can Overactive Apoptosis be desirable?

A

–Returns cell populations to normal after challenge
–Neutrophil apoptosis during inflammation
–CTL death

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

What are the characteristics of apoptosis?

A 
Tightly controlleed/ programmed 
Cell shrinkage
•Organelle integrity
•Chromatin condensation
•Plasma membrane integrity
  • Thermodynamics uphill
  • Internal control
  • Purposeful
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What are the characteristics of necrosis?

A 
Not tightly controlled (accidental/random), caysed by external factors 
•Cell swelling
•Organelle disruption
•Nuclear swelling
•Plasma membrane rupture
  • Thermodynamics downhill
  • External “control”
  • Accidental
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Caspases

A
  • Cysteinyl ASPartate-specific proteASES
  • Key cysteine in active site QACxG
  • Aspartate at P1 of substrate tetrapeptide
  • Tetrapeptide defines caspase specificity
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Three broad categories of caspases

A
  1. Inflammatory caspases
  2. Initiator caspase
  3. Effector caspase
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Inflammatory caspases

A
  • Maturation of pro-inflammatory cytokines

* e.g. Caspases 1, 4, 5, 11, 12, 14

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Initiator caspase

A
  • Kick off the caspase cascade

* e.g. Caspase 8, 9

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Effector caspase

A
  • Cleavage of cellular substrates
  • Mediate the killing
  • e.g. Caspases 3,6, 7
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Describe the activation of Caspases

A

•Caspases are produced as inactive zymogens
•Pro domain 23 - 220aa
–large pro-domain = initiator caspase (contains recruitment domains)
–Small pro-domain = executioner caspase
•Activation requires a minimum of 2 cleavages
Cleavage at the prodomain and formation of a tetramer

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Cleavage of caspase substrates during apoptosis: what is the function of caspases?

A
  1. Pro-caspase (inactive) → active caspase
  2. Break down Structural proteins and DNA replication/repair enzymes
  3. Inactive nuclease → active nuclease
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

What is CAD?

A

caspase-activated DN-ase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

What is ICAD?

A

inhibitor of CAD (caspase substrate)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

End goal of apoptosis

A

detach cell from neighbours
Dismantle cell
destroy DNA
alter the cell surface

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Cell suicide occurs in response to

A

cellular insults

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Extrinsic Pathway

A

–Cell are instructed to die from outside
–Receptors (“Death Receptors”) on cell surface induce death when ligated

  1. Killer lymphocyte have a protein (fas ligand) on their surface
  2. Fas death receptor on pre apoptotic cell recognises the fas ligand
  3. Recruitment of FADD (adaptor protein) which has a death domain and a death effector domain
  4. Death domain joins the intracellular Fas death receptor
  5. Death effector domain recognised by caspases (8 or 10)
  6. FADD recruits procasapases which leads to initiation and activation of procaspases via cleavage
  7. Caspase cascade takes place
  8. Resulting in an apoptotic cell
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Intrinsic pathway
- cytochrome c released into the cytoplasm from damaged cell which binds to Apaf-1 (adapter protein) - this recruits inactive procaspases - activates then - caspase cascade initiated
26
Adaptor molecules are important in
recruiting initiator caspases and allowing their activation
27
Control of cell death - Bcl-2 family
•Family of interactive proteins * Protect from apoptosis – Pro-survival * Suppress protection – Pro-death * Pro- death and pro-survival members * Bcl-2 - prototypic member of the family
28
Bcl-2 Pro-survival members
•For example: –Bcl-2 •Crucial for cell survival •Essential for life
29
Bcl-2 Pro-apoptosis members = Pro-death | Divided into 2 categories
Bax-like = BH123 members –lack BH4 domain (BH123) –form pores in mitochondria →release of Cyt c BH3 only – also called ‘Bad’ proteins –central to life & death decisions of a cell –activation during stress will dictate the outcome
30
Bcl-2 Mechanism of Action
Guard mitochondrial integrity - Regulate Cyt c release LIFE Bcl-2 & Bax balance
31
DEATH
BH3 only members disrupt the balance | Bax will form pores in mitochondria
32
LIFE
Bcl-2 & Bax balance
33
Bcl-2 prevents
mitochondrial disruption
34
BH3 only proteins inhibit
Bcl-2 & tip the balance
35
Control of Apoptosis: balancing act
•Pro v Anti-apoptosis signals •Balance can be tipped by cell stress –e.g. genotoxic damage can stabilise p53 and lead to transcription of pro-death members
36
IAPs
–Inhibitors of apoptosis –produced by certain viruses to prevent death –Inhibit caspases via inhibition of •activation of pro-caspases •activity of active caspases
37
The ultimate step in cell death
* “Burial” * Cell surface changes act as “eat me” signals (recognised by phagocytes) * Viable cells eat the dying cell safe and controlled removal of cells prevents apoptotic cells falling apart intracellular contents are detrimental Cell Removal is the aim of apoptosis
38
Apoptotic Cell Surface Changes (that are recognised by the phagocyte)
Redistribution of membrane lipids (especially phosphatidylserine)
39
Receptors on phagocytes
* Recognise apoptosis-induced surface changes * Apoptotic cells are eaten and degraded * A silent process •Safe packaging –failure leads to inflammation
40
Biochemical/Cell Biological Features in apoptosis
``` •Ligation (FAS ligand) of surface death receptors –Generates a death-inducing signalling complex •Mitochondrial Changes –Release of cytochrome c •Cysteine Protease Activity –Protein cleavage after aspartate residues •DNA cleavage –Activation of nucleases (CAD) –Cleavage of DNA into fragments •Surface changes –“eat me signals” –Flip-out of phosphatidylserine •Phagocytosis ```
41
How often does cell death occurs
Up to 1million times in some tissues
42
Phase 1
1. Presence of signal 2. Intracellular signalling pathways activated or disrupted 3. Epopotosis machinery employed (caspase cascade) 4. Phagocyte degradation
43
Phase II
1. Extracellular Signals: Cytosine deprivation, gentoxdic (chemical or radiation) DNA damage, death receptor ligation 2. Intracellular signals: p53 transcribed, survival signals , caspase 3. Both activate the apoptosis engine (caspase cascade)
44
Which amino acid forms the active site of caspase?
Cysteine 1
45
Are caspases always activated
No | Only when cells becomes apoptosis
46
CNS caspases activate other caspases?
Yes | In turn the activated caspases can activate others
47
What does a small prodomain indicate?
An effector caspase
48
Are procaspases active or inactive?
Inactive
49
What are the 4 domains I’d the Bcl-2 family?
BH4 BH3 BH1 bH2
50
Describe apoptotic cell surface changes
These changes are recognised by phagocytes - In a healthy cell membrane the phosphadityl serine are facing the cytosol - When the cell become apoptotic some of the phosphadityl serine face the Extracellular space due to a biochemical change
51
What type of caspase has a large prodomain?
Initiator casapase
52
What are the 3 main caspase domains?
Prodomain Large domain Small domain
53
What are the 3 main caspase domains?
Prodomain Large domain Small domain
54
Which caspase has a small prodomain?
Effecror casapa
55
Where do caspases cleave proteins?
At the P1 aspartase
56
How does capsase activation occur?
1) Cleave of the prodomain 2) Cleavage and separation of the large/ small domains 3) joining of 2 capspases to form a tetramer
57
Which end of the protein is the small domain?
Carboxyl end
58
Which end of the protein is the prodomain?
Amino
59
Do the survival members of the Bcl-2 family have all 4 domains?
Yes
60
Which domains do the Bcl-2 pro death members have?
BH123
61
What would be the effect of an upregulation of BH3?
Induce apoptosis
62
How does Bcl-2 disrupt mitochondria?
1. They have BH123 on their surface (inactive) 2. Apoptotic stimulus 3. BH123 complex changes in conformation and makes a pore in the mitochondrion 4. Mitochondrion releases cytochromes
63
When is BH123 inactive?
Pro-survival Bcl-2 protein blocks pore formation | An Apoptotic stimulus can replace the Bcl-2 protein thus allowing the BH123 to become a pore

Cell Biology (BY1CB1) (16 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2025 Bold Learning Solutions. Terms and Conditions