PHAL 311 revision - apoptosis and necrosis

what triggers necrosis

when cells are exposed to severe harmful stimuli such as toxins, infection, injury, ischemia (loss of blood supply) or inflammation.

what is the key feature of necrosis?

it loses the ability to maintain membrane integrity. maintaining the membrane requires energy (ATP), and when the cell is damaged it loses ATP production, meaning it cannot maintain ion gradients or its cytoskeleton. This causes water to rush into the cell, causing swelling

morphological features of necrosis (3):

• cell swelling - blebs

• vacuolization - formation of vacuoles (small membrane bound sacs)

• plasma membrane rupture (lysis)

what are necrotic blebs and what results because of them?

bubble-like protrusions of the membrane caused by cytoskeletal breakdown. The blebs expand until the membrane bursts. When the membrane ruptures, its intracellular contents (including proteases and other damaging enzymes) spill into surrounding tissue.

why does necrosis cause inflammation?

Necrotic debris is not efficiently cleared because the dying cell does not display the proper “eat me” signals that phagocytes recognise. therefore the immune system responds aggressively, producing inflammation

What is apoptosis and what is the key feature of it?

an organised and energy-dependent form of cell death. In apoptosis, the cell still has enough ATP to carefully dismantle itself

key morphological features of apoptosis (5)?

• cell shrinking

• chromatin condensation

• membrane remains intact

• budding and packaging of contents

• formation of apoptotic bodies

what is chromatin condensation in apoptosis?

during apoptosis, DNA becomes tightly packed into dense clumps. this happens because the cell is shutting down gene activity and preparing the nucleus for fragmentation

what are apoptotic bodies in apoptosis?

apoptotic bodies are small membrane-bound fragments containing nuclear and cytoplasmic material. they form when the cell breaks apart in an organised way, allowing immune cells to engulf them easily. because the membrane remains intact, harmful enzymes do not leak out, so inflammation is avoided

what are the two major pathways through which apoptosis can occur?

intrinsic and extrinsic pathway

what is the extrinsic pathway of apoptosis?

1. extracellular environmental signals

2. death ligands (such as Fas, TNF-α or TRAIL) bind to death receptors (Fas receptor, TNF receptor)

3. these receptors contain death domains, which recruit adaptor proteins such as FADD and TRADD

4. this complex activates pro-caspase-8, converting it into active caspase-8

5. caspase-8 then cleaves pro-caspase-3 into active caspase-3, which triggers apoptosis

what is the intrinsic pathway of apoptosis?

1. the intrinsic pathway is triggered by internal signals such as DNA damage, oxidative stress, or lack of survival signals

2. pro-apoptotic proteins such as Bax damage the mitochondrial membrane, making it leaky

3. this causes the release of cytochrome C, which binds to Apaf-1, forming a complex that actives caspase-9

4. caspase-9 then cleaves pro-caspase-3 into caspase-3, which triggers apoptosis

what are caspases and what is their main function?

are cysteine aspartate proteases (protein digesting enzymes) that cleave proteins after aspartic acid residues → key regulators of apoptosis

what is the function caspase inhibitors? give an example of one and what it does:

are used to prevent or reduce cellular apoptosis, eg. inhibitor of apoptosis proteins (IAPs) that inhibit caspase 3

what is the Bcl-2 family

protein family that regulates the permeability of the mitochondrial outer membrane, allowing cytochrome C to escape

give examples of anti-apoptotic Bcl-2 family members (2)

Bcl-2, Bcl-XL

what is a drug that falls under the anti-apoptotic Bcl-2 family and how does it work?

deprenyl → it upregulates DIP-1 which is a Bcl-XL homologue

give examples of anti-apoptotic Bcl-2 family members (3)

Bax, Bid, Bad