Apoptosis

Question 1

What is apoptosis?

Answer 1

It is a programmed cell death based on suicide pathway enzymes leads to degrading cell’s nuclear DNA and nuclear and cytoplasmic proteins

Question 2

Apoptosis in physiologic situations

Answer 2

1. Eliminate no longer needed cells
2. Maintain steady number of cell population in tissue

Question 3

Apoptosis in pathologic conditions

Answer 3

1. Genetically altered cells
2. Injured beyond repair cells

Question 4

Apoptosis is blocked in ………………… and there is little of or no …………………. during apoptosis because ………

Answer 4

Cancer cells, inflammation ( without eliciting host reaction ) , apoptotic bodies are quickly phagocytosed

Question 5

Examples of physiologic apoptosis

Answer 5

1. Apoptosis during embryogenesis
2. Hormone deprivation
3. Cell loss of proliferating cell populations
   4.death of cells that have served their useful purposes

Question 6

Embryogenesis

Answer 6

Apoptosis occurs during :
1. Implantation
2.organogenesis
3.developmental involution
4. Metamorphosis

Question 7

Involution of hormone dependent tissues :

Answer 7

1. Menstrual cycle : endometrial cells breakdown
   2.After weaning : regression of lactating breast

Question 8

Cell loss in proliferating cell population

Answer 8

As in intestinal crypt epithelia to maintain a constant number of

Question 9

Apoptosis of cells that have served their purposes as :

Answer 9

1. Neutrophils in acute inflammation
2. Lymphocytes at the end of immune response

Question 10

Apoptosis in pathologic conditions examples

Answer 10

1. Any cell that has irreparable DNA damage
   2.Any cell that has accumulated misfolded proteins
2. Any cell that has viral infection
3. Atrophied cells in parenchymal organs

Question 11

DNA damage

Answer 11

• it can occur directly or via production of Free Radials
• by radiation, extreme high temperatures, hypoxia , cytotoxic anticancerous drugs

Question 12

Accumulation of misfolded proteins

Answer 12

Due to mutations or free radicals

Question 13

Viral infections trigger apoptosis by :

Answer 13

1. The virus itself as in adrenovirus and HIV
   2.host immune response as in viral hepatitis

Question 14

Pathologic atrophy in parenchymal organs occur due to

Answer 14

Duct obstruction as atrophy happens in pancreas , liver and parotid gland .

Question 15

Initiation and Mechanism of apoptosis

Initiation of apoptosis

Answer 15

1.Extrinsic Pathway = Receptor-ligand pathway
2. Intrinsic pathway = mitochondrial pathway

Question 16

External factors of apoptosis

Answer 16

Nutrient loss, Radiation , heat and activation of death receptors on the surface of cell membrane by THF and FAS 3 , all are external triggers .

Question 17

Internal factors of apoptosis

Answer 17

• it depends on the “ increase in mitochondrial permeability “
  -this increase occurs due to misfolded proteins and deregulated signals. ( they considered to be internal factors .

Question 18

Intrinsic pathway of apoptosis

Answer 18

1. BCL-2 family sensors recognise the internal factor
2. Activation of BCL-2 family effectors (BAX & BAK )
3. These effectors alter mitochondrial permeability
4. Release of pro-apoptotic proteins as Cytochrome C
5. These proteins affect caspases
6. Endonuclease activation and breakdown of cytoskeleton
7. Formation of cytoplasmic bleb
8. Alternation to apoptosis body
9. Phagocytosis of this body

Question 19

Extrinsic pathway of apoptosis

Answer 19

1. Ligand binds to the death receptors
2. Activation of adaptor proteins
3. Caspase activation
4. Endonuclease activity and breakdown of cytoskeleton
   5.apoptotic bleb formation
5. Apoptotic body formation
   7.Phagocytosis

Question 20

Apoptosis is initiated by :

Answer 20

The interaction of pro-apoptotic and anti-apoptotic bodies in the BCL-2 family , including BAK and BCL-2.

Question 21

Apoptosis is mediated by :

Answer 21

Caspases

Question 22

What are caspases?

Answer 22

1. Proteolytic enzymes ( Cleaving proteins activity )
2. Activate other proteins that degrade
   cytoskeleton , organelles and DNA .
3. They exist in cells as pro caspases ( inactive form )
   4 then , activated by cleavage of other caspases

Question 23

The initiation of apoptosis is …………………. Because once it begins ……..

Answer 23

Tightly regulated , it leads to cell death

Question 24

Morphology of apoptosis :

Answer 24

1. Oval or round mass with intensely eosinophilic cytoplasm
2. Nuclei show pyknosis and karyorrhexis

Question 25

Normal role of P53 gene

Answer 25

• It arrests cell cycle at G1 phase to allow time for the repair of the damage
• after successful repairing , it allows cell cycle progression from G1 to S phase .

Question 26

Role of P53 gene in apoptosis

Answer 26

It triggers apoptosis by activating bax and BAK if the DNA damage is reparable .

Question 27

Absence of P53 gene

Answer 27

DNA damaged cells are allowed to survive resulting in mutations and translocations leading to neoplastic transformation