Apoptosis

What are the types of cell death?

Apoptosis

Necrosis

What causes Necrosis?

Response to non physiological/pathological conditions that disrupt homeostasis

Membrane dissolution due to osmotic lysis/shear stress

causes inflammatory responses

What are features of necrosis?

ER swelling, mitochondrial swelling, matrix densities, clumping of chromatin, bleb formation-reversible

lysis of ER, lysosome rupture, large matrix densities, karyolysis-irreversible

What is apoptosis?

Programmed cell death by gene expression and followed by phagocytosis

removal of specific cells for development, tissue remodelling, cancer, infection

What are the three phases of apoptosis?

Death stimulus dependent (lack of growth factors, shortage of metabolic supply..)

Effector phase

degradation stage, end stage apoptosis

What changes occur during apoptosis?

Loss of membrane symmetry blebbing

cytoplasmic shrinkage

loss off mitochondrial membrane potential

nucleus condensation

disruption of nuclear envelope

clumping of chromatin

formation of apoptotic bodies

What are caspases?

Apoptosis is dependent on activation of caspases

Caspases are cysteine proteases

inactive pro-caspases are activated via adaptor proteins

causes cascade involving initiator and effector caspases

How does extrinsic/receptor mediated death pathway work?

FAS ligand binds to FAS with FADD

this alongside pro-caspase 8 starts the death inducing signalling complex (DISC)

produces caspase 8 (may be inhibited by FLIP)

produces caspases 3,6,7 (may be inhibited by IAP)

this causes proteolysis

What is the process of mitochondrial death signalling pathway?

Bcl proteins regulate ion channels in mitochondria

can be anti-apoptotic or pro

either prevents pore opening and cytochrome c loss , or keeps pores open to allow cytochrome c loss usually due to DNA or cell damage

cytochrome C causes pro-apoptotic pathways

causes activation of pro-caspase via APAF-1 can be stopped by Act

How can we identify apoptosis?

DNA laddering, TUNEL staining

Examples of apoptosis in action?

Metamorphis-frogs, C.elegans

Organogenesis

Mammary gland after weaning

Intestinal villi