What is apoptosis?
It is a programmed cell death based on suicide pathway enzymes leads to degrading cell’s nuclear DNA and nuclear and cytoplasmic proteins
Apoptosis in physiologic situations
- Eliminate no longer needed cells
- Maintain steady number of cell population in tissue
Apoptosis in pathologic conditions
- Genetically altered cells
- Injured beyond repair cells
Apoptosis is blocked in ………………… and there is little of or no …………………. during apoptosis because ………
Cancer cells, inflammation ( without eliciting host reaction ) , apoptotic bodies are quickly phagocytosed
Examples of physiologic apoptosis
- Apoptosis during embryogenesis
- Hormone deprivation
- Cell loss of proliferating cell populations
4.death of cells that have served their useful purposes
Embryogenesis
Apoptosis occurs during :
1. Implantation
2.organogenesis
3.developmental involution
4. Metamorphosis
Involution of hormone dependent tissues :
- Menstrual cycle : endometrial cells breakdown
2.After weaning : regression of lactating breast
Cell loss in proliferating cell population
As in intestinal crypt epithelia to maintain a constant number of
Apoptosis of cells that have served their purposes as :
- Neutrophils in acute inflammation
- Lymphocytes at the end of immune response
Apoptosis in pathologic conditions examples
- Any cell that has irreparable DNA damage
2.Any cell that has accumulated misfolded proteins - Any cell that has viral infection
- Atrophied cells in parenchymal organs
DNA damage
- it can occur directly or via production of Free Radials
- by radiation, extreme high temperatures, hypoxia , cytotoxic anticancerous drugs
Accumulation of misfolded proteins
Due to mutations or free radicals
Viral infections trigger apoptosis by :
- The virus itself as in adrenovirus and HIV
2.host immune response as in viral hepatitis
Pathologic atrophy in parenchymal organs occur due to
Duct obstruction as atrophy happens in pancreas , liver and parotid gland .
Initiation and Mechanism of apoptosis
Initiation of apoptosis
1.Extrinsic Pathway = Receptor-ligand pathway
2. Intrinsic pathway = mitochondrial pathway
External factors of apoptosis
Nutrient loss, Radiation , heat and activation of death receptors on the surface of cell membrane by THF and FAS 3 , all are external triggers .
Internal factors of apoptosis
- it depends on the “ increase in mitochondrial permeability “
-this increase occurs due to misfolded proteins and deregulated signals. ( they considered to be internal factors .
Intrinsic pathway of apoptosis
- BCL-2 family sensors recognise the internal factor
- Activation of BCL-2 family effectors (BAX & BAK )
- These effectors alter mitochondrial permeability
- Release of pro-apoptotic proteins as Cytochrome C
- These proteins affect caspases
- Endonuclease activation and breakdown of cytoskeleton
- Formation of cytoplasmic bleb
- Alternation to apoptosis body
- Phagocytosis of this body
Extrinsic pathway of apoptosis
- Ligand binds to the death receptors
- Activation of adaptor proteins
- Caspase activation
- Endonuclease activity and breakdown of cytoskeleton
5.apoptotic bleb formation - Apoptotic body formation
7.Phagocytosis
Apoptosis is initiated by :
The interaction of pro-apoptotic and anti-apoptotic bodies in the BCL-2 family , including BAK and BCL-2.
Apoptosis is mediated by :
Caspases
What are caspases?
- Proteolytic enzymes ( Cleaving proteins activity )
- Activate other proteins that degrade
cytoskeleton , organelles and DNA . - They exist in cells as pro caspases ( inactive form )
4 then , activated by cleavage of other caspases
The initiation of apoptosis is …………………. Because once it begins ……..
Tightly regulated , it leads to cell death
Morphology of apoptosis :
- Oval or round mass with intensely eosinophilic cytoplasm
- Nuclei show pyknosis and karyorrhexis
