Programmed cell death is known as apoptosis

1. APOPTOSIS

2. APOPTOSIS
Apoptosis was first recognized in 1972 by its
characteristic morphology, and was named after the
Greek word 'apoptosis‘ meaning 'a falling away
from' (G. apo = away from; G. ptosis =falling).
Defined as Programmed cell death in which there is
death of individual cells without inciting
inflammatory processes.
In embryogenesis and normal growth, physiologic
cell death occurs which may be referred as
programmed cell death or apoptosis.
Apoptosis can also occur in pathological diseases.

3.  Mechanism of Apoptosis
There are two processes:
1. Initiation phase mediated by
2. Execution phase in which enzymatic
degradation leads to cell death

4. 1. INITIATION PHASE
There are two pathways of initiation of
apoptosis:
a) Extrinsic receptor initiated pathway
b) Intrinsic mitochondrial pathway

5. These two pathways are interconnected and
converge to activate caspases
a) EXTRINSIC PATHWAY:
On cross linkage of Fas (Death domain) by its
ligand three or more molecules come together
and bind to cytoplasmic Fas-associated death
domain (FADD) which in turn binds to inactive
forms of caspase-8 via death domain.

6. b) INTRINSIC MITOCHONDRIAL PATHWAY :
There are more than 20 antiapoptotic proteins.
Of which Bcl-2 and Bcl-x are located on the
mitochondrial membrane of cytoplasm.
Bcl-2 and Bcl-x are replaced when cells are
deprived of survival signals or stress by
proapoptotic members like Bak, Bax and Bim.
 This leads to increased mitochondrial
membrane permeability and release of several
proteins which activate caspase cascade.

7. 2. EXECUTION PHASE
• The final proteolytic cascade is mediated by the
proteases (Caspase: ‘c’- cystine protease that cleaves
aspartic acid residues).
• There are more than 10 members in caspase family
which are grouped into initiator and executioner
groups depending on their order in which they are
activated during apoptosis e.g. caspase-8 and 9 are
initiator caspases and caspase-3 and 6 are
executioner caspases.
• These caspases are hydrolysed autocatalytically
following cleavage of initiator caspase to generate the
active form.
• The enzymatic death programme sets in motion by
rapid and sequential activation of other caspases.

8. • These caspases can act on many cellular
components like cytoskeleton and nuclear
matrix proteins.
• Cytoskeleton destruction and nuclear break
down occurs.
• Caspase target proteins of transcription, DNA
replication and DNA repair in the nucleus e.g.
caspase-3 activates cytoplasmic DNAs.
• Not only gross changes, but microscopical
changes are also not obvious since single cell
death occurs.

9. 1. Shrinkage of individual cells: cells-size smaller,
cytoplasm is dense and organelles are tightly packed.
2. Condensation of chromatins: Most characteristic in
apoptosis. Aggregation of chromatins under nuclear
membrane with variable shape and size (Semilunar
shape)
3. Cytoplasmic fragmentation
4. Cytoplasmic buds containing fragments of nucleus:
Cytoplasm shows excessive surface budding and
formation of membrane bound fragments (Apoptotic
bodies) containing cytoplasm and tightly packed
organelles with or without nuclear fragments. Nucleus
itself may break up into two or more fragments.
5. Presence of apoptotic bodies in the adjacent cells and
phagocytes