intrinsic and extrensic pathway

1. Apoptosis
Shivam patel

2. What is apoptosis?
 A process of programmed cell death that occurs in multicellular organisms.
Biochemical events lead to characteristic cell changes (morphology) and
death.
 These changes include blebbing, cell shrinkage, nuclear fragmentation,
chromatin condensation, chromosomal DNA fragmentation, and global mRNA
decay. Between 50 and 70 billion cells die each day due to apoptosis in the
average human adult.

3. Cell death
 Cell die by one of two
mechanisms-
Necrosis – Death by injury
pathological cond.
Apoptosis- Death by suicide
physiologiacal cond.

4. Importance of apoptosis
 Apoptosis is needed for proper development
 It shapes the embryo of every animal and is
behind the spectacular transformations of
caterpillars into butterflies and tadpoles into
frogs.
 It`s needed to destroy cell
 Cells infected with viruses
 Cancer cell
 Immune system
 IL-2
 Fas ligand
 TNF factor

5. What is caspases?
 Caspases are a family of protease enzymes
playing essential roles in programmed cell death
(including apoptosis, pyroptosis and necroptosis)
and inflammation.
 It contains an N-terminal and C terminal domain,
a small subunit and a large subunit (similar to a
ribosome)
 Type of Caspases
 Inflammatory Caspases: -1, -4, and -5
 Initiator Caspases: -2, -8, -9, and -10
 Effector Caspases: -3, -6, and -7

6. Two type of Caspase Pathways
 1. Intrinsic Pathway
 It`s characterized by permeabilisation of
the mitochondria and release of cytochrome c into
the cytoplasm.
 Initiated from within the cell.
 Activated in response to signals such as DNA
damage,loss of cell survival factors cell stress.
 Hinges on balance between pro and antipoptotic signal
of Bcl-2 family.
 Apaf-1 ,cytochrome-c,ATP(apoptosome)activate
procaspase-9 complex.
 Pro apoptotic protins released which activate caspase
proteases.

7. Extrinsic pathway.
 It`s activated by extracellular ligands binding to
cell-surface death receptors, which leads to the
formation of the death-inducing signaling complex
(DISC).
 A cell initiates intracellular apoptotic signaling in
response to a stress, which may bring about cell
suicide.

9. IAPs-Inhibitor of Apoptosis Proteins
 Inhibitors of apoptosis are a group of proteins that mainly act on the intrinsic
pathway that block programmed cell death,which can frequently lead
to cancer or other effects for the cell if mutated or improperly regulated.
 Many of these inhibitors act to block caspases, a family of cysteine
proteases that play an integral role in apoptosis.
 Some of these inhibitors include the Bcl-2 family, viral inhibitor crmA, and
IAP's.

10. Apoptpsis role in disease cancer
 Exam.
 Some B-Cell Leukemia and Lymphomas express hingh levels of Bcl-2,thus
blocking apoptotic signals the may receive.
Thw high level result from a translocation of the BCL-2 gene into a
enance region foe antibody production.
 Melanoma(the most dangerous type of skin cancer)
cell avoid apoptosis by inhibiting the expression of the gene encoding
Apaf-1

11. Thank you