Topic 7 - Cell Death Flashcards Preview

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Flashcards in Topic 7 - Cell Death Deck (33):
1

What is programmed cell death?

A type of cell death where particular cells die in a reproducible, controlled manner as a result of the action of proteins encoded by the cells themselves. Because of its predictable nature, this form of death was believed to occur as the result of a death 'programme', and so was named programmed cell death. Well-known examples are the loss of the cells between digits (e.g. during the development of fingers), and in the tail of the tadpole, when it metamorphoses into a frog. In adult tissues, cell death usually balances cell division, ensuring that tissues and organs retain the same size and structure as old cells are replaced.

2

What is apoptosis?

A type of programmed cell death that removes cells without causing inflammation. Characterised by cell shrinkage, membrane blebbing, chromatin condensation, DNA fragmentation and activation of caspase enzymes.

3

What is necrosis?

Typical response of cells to injury in the form of harmful reagents, infections or wounds. The damaged cell swells because the cell membrane fails to control the passage of ions and water, and finally lyses (bursts), releasing its contents, which in vertebrates can stimulate a potentially damaging inflammatory response.

4

What is cell membrane blebbing?

In relation to cell membranes - the formation of membrane protrusions, involving detachment of the cell membrane from cytoskeletal components. A feature of apoptotic cell death and, in some cases, necrotic cell death.

5

What are DAMPs?

Damage-associated molecular pattern molecules. Inflammatory molecules that are lost from leaky necrotic cells.

6

What is an apoptosome?

A multi-protein complex formed by the association of cytochrome c, dATP and Apaf-1. The binding of procaspase 9 to the apoptosome leads to dimerisation and activation of procaspase 9 monomers, thereby triggering the caspase activation cascade.

7

What is AMP-activated protein kinase (AMPK)?

A protein kinase that plays a central role in cellular energy homeostasis. AMPK is activated when the cytosolic concentration of adenosine monophosphate (AMP) increases.

8

What is mitophagy?

A form of autophagy where dysfunctional or unwanted mitochondria are digested.

9

What are reactive oxygen species (ROS)?

Collective term for both oxygen-based radicals (such as nitric oxide) and reactive non-radical oxidants (such as hydrogen peroxide (H2O2) and lipid peroxide). ROS are generated as by-products of oxidative metabolism and other cellular reactions. They are potentially damaging to cells, because they cause oxidative damage to macromolecules and membranes.

10

What is mPT (mitochondrial permeability transition)?

mPT or mitochondrial permeability transition marks a sudden increase in the flux of ions and solutes across the inner mitochondrial membrane. This leads to mitochondrial swelling and rupture, which precipitates necrotic cell death.

11

During an adaptive immune response, there is a massive proliferation of the specific types of lymphocytes (white blood cells) needed to overcome an infection. What do you think would happen to the cells once the infection is over?

Once the infectious agents have been destroyed, the lymphocytes are no longer needed. Some of them differentiate into memory cells, but the majority are removed by apoptosis.

12

During nervous system development, sufficient neurons must be generated to innervate their target tissue. The formation of appropriate neuronal connections is ensured by the production of excess neurons during early development. What do you think would happen to those neurons that do not form connections during development?


The neurons that do not form connections with other neurons or target tissues die via apoptosis and are removed. This ensures that only connected neurons are retained.

The neurons that form connections receive signals that promote cell survival, whereas those cells that do not form connections undergo apoptosis by default.

13

What are caspases?

Cysteine-dependent aspartate-directed proteases. A family of proteases that all contain cysteine at their catalytic sites, and cleave their protein substrates on the carboxyl side of aspartate residues. Caspases are present in cells as inactive precursors (zymogens) known as procaspases. Initiator caspases activate effector caspases, which in turn hydrolyse specific proteins thereby committing a cell to die.

14

Define pro-apoptotic

The term used to describe events, or regulatory proteins, that promote apoptosis.

15

What are initiator caspases?


Caspases that, when activated, trigger apoptosis. They activate effector caspases, which hydrolyse cellular proteins

16

What are effector caspases?

Caspases that are activated by initiator caspases and go on to hydrolyse cellular proteins and thereby trigger cell death.

17

What is DNA fragmentation factor?

A caspase-activated nuclease that hydrolyses genomic DNA during apoptosis.

18

What are death receptors?

Cell surface receptors to which ligands that activate the extrinsic apoptotic pathway bind. The ligands may be secreted factors or molecules expressed on the surface of other cells.

19

What is the death-inducing signalling complex (DISC)?

A multiprotein complex that is formed by recruitment of adaptor proteins to death receptors upon ligand binding. The complex recruits initiator procaspase molecules, which are autoactivated.

20

What is the Fas signalling pathway?

An apoptotic signalling pathway. When Fas ligand binds to Fas it triggers the extrinsic apoptosis pathway.

21

What is the death domain?

A domain within the intracellular part of a death receptor molecule.

22

What is DNA fragmentation factor?

A caspase-activated nuclease that hydrolyses genomic DNA during apoptosis.

23

What are death receptors?

Cell surface receptors to which ligands that activate the extrinsic apoptotic pathway bind. The ligands may be secreted factors or molecules expressed on the surface of other cells.

24

What is the death-inducing signalling complex (DISC)?

A multiprotein complex that is formed by recruitment of adaptor proteins to death receptors upon ligand binding. The complex recruits initiator procaspase molecules, which are autoactivated.

25

What is the Fas signalling pathway?

An apoptotic signalling pathway. When Fas ligand binds to Fas it triggers the extrinsic apoptosis pathway.

26

What is the immunological synapse?

The interface between a cytotoxic T lymphocyte and a target cell.

27

The apoptosome is functionally equivalent (although structurally very different) to another caspase activation complex that you have encountered in this topic. Can you recall the name of that complex, and identify similarities between it and the apoptosome?

The apoptosome is functionally equivalent to the DISC. They are both multi-protein complexes that recruit initiator procaspases through homotypic protein–protein interactions. Both complexes lead to caspase activation through the formation of initiator procaspase dimers, procaspase 8 (or 10) dimers in the case of the DISC, and procaspase 9 dimers in the case of the apoptosome.

28

What kind of cell death would result from loss of cell membrane integrity?

Necrosis

29

What is the Granzyme pathway?

The granzyme pathway involves the release of vesicles containing proteolytic enzymes onto a target cell. The proteolytic enzymes are liberated inside the target cell and go on to cleave various substrates that lead to apoptotic cell death.

30

What is the Extrinsic apoptosis pathway?

The extrinsic apoptosis pathway is activated by the binding of extracellular stimuli to death receptors on the surface of a target cell.

31

What does the activation of death receptors lead to?

The activation of death receptors leads to the formation of a caspase activation complex called the DISC. The downstream consequences of DISC formation depend on the cell type, and whether it uses the Type I or II extrinsic apoptosis mechanism.

32

Explain the role of caspase 8 in the extrinsic apoptosis pathway.

In some cells, caspase 8 is activated by the DISC in sufficient amounts to cause apoptosis. In other cells, caspase 8 cleaves the Bcl-2 family member Bid. The truncated Bid protein (tBid) triggers permeabilisation of the outer mitochondrial membrane by directly activating the pro-apoptotic Bcl-2 family member Bax.

33

What is the Intrinsic apoptosis pathway?

The intrinsic apoptosis pathway is activated by numerous cell stressors. The effect of a particular stressor is specifically conveyed by one or more BH3-only proteins of the Bcl-2 family.

The intrinsic apoptosis pathway depends on MOMP and formation of apoptosomes to activate caspase 9.