8. These electron micrographs show cells that have died by (A) necrosis or (B and C) apoptosis. The cells in
(A) and (B) died in a culture dish, whereas the cell in (C) died in a developing tissue and has been
engulfed by a neighboring cell. Note that the cell in (A) seems to have exploded, whereas those in (B) and
(C) have condensed but seem relatively intact. The large vacuoles visible in the cytoplasm of the cell in
(B) are a variable feature of apoptosis.
9. MECHANISM
The Intracellular machinery are responsible
for apoptosis.
Machinery depends on a family of
proteases called caspases.
They have a cysteine at their ‘active site’ &
and cleave their target specific aspartic
acids.
Cysteine Aspartic
10.
11. 1
.
Capase are synthesized
in the cell as inactive
form of
procaspase.
MECHANISM
These procaspases are
activate by cleavage at
aspartic acids by other
caspase.
2
.
Once its activated they
cleave and there by
activate other procaspases
resulting in an amplifying
proteolytic cascade.
3
.
They have ability to degrade
target cell proteins and some
caspase are nuclease that
degrades DNA.
4
.
The protease cascade is
not only destructive and
self amplifying but also
irreversible.
5
.
12. 2 TYPES OF PATHWAY
EXTRINSIC
PATHWAY
Procaspase
activation can be
triggered from
outside the cell by
activation of death
receptor on the cell
surface.
1.
INTRINSIC
PATHWAY
Procaspase
activation can
be initiate
under cell.
2.
14. EXTRINSIC PATHWAY
o Fas protein binds with intracellular “adaptor proteins”
that aggregate with procaspase 8 molecule and make
complex.
o Kiiler Lymphocyte producing a protein called
Fas ligand.
Then caspase 8 molecule is activated by cleave one
another and they are activate other downstream
procaspase and induce apoptosis.
Fas ligand binds with Fas protein of death receptor
on the surface of target cell.
By extracellular stimuli
16. INTRINSIC PATHWAY
o When cells are damaged or stressed they can also kill
themselves by triggering procaspase activation from
within the cell.
o Eg. If mitochondria are injured they are induced to
release the electron carrier protein cytochrome c into
cytosol.
By extracellular stimuli
o Where its bind and activate adaptor protein called Apaf
– 1.
o Aggregation of Apaf 1 and binding of ‘procaspase – 9’.
o Activation of procaspase – 9 and make Caspase
Cascade.
o Apoptosis.
17. These protein belongs to Bcl-2 protein
family.
This response usually require p53 protein
which can recognize damaged - DNA and
activates the transcriptions of genes that
encode proteins that promote the release of
cytochrome – 6 from mitochondria.
18. • Bcl-2
family
Some members of this
family
Bcl-2
itself
Main Intracellular Regulator of Cell Death
Program
• IAP
Bcl-Xl Inhibit apoptosis by blocking the release of
cytochrome c from mitochondria.
APOPTOSIS INHIBITING
MEMBER
● Bax
● Bak
Promote procaspase activation and cell death stimulate
the release of cytochrome c
APOPTOSIS PROMOTING
MEMBER
If the gene encoding Bax and Bak are both inactivated cells
are remarkably resistant to most apoptosis inducing stimuli.
19. INHIBITOR OF APOPTOSIS
1. They bind to some procaspase to
prevent their activation.
2. They bind to caspase to inhibit their
activity.
These proteins are inhibit apoptosis in two
ways:-
(IAP family)
20. IMPORTANC
E
Cell death balances the cell
division.
(A) The paw in this mouse embryo has been
stained with a dye that specifically
labels cells that have undergone
apoptosis. The apoptotic cells appear as
bright green dots between the
developing digits. (B) This interdigital
cell death eliminates the tissue between
the developing digits, as seen one day
later, when few, if any, apoptotic cells
As a tadpole changes into a frog, the cells in
the tadpole tail are induced to undergo
apoptosis; as a consequence, the tail is lost.
All the changes that occur during
metamorphosis, including the induction of
apoptosis in the tail, are stimulated by an
increase in thyroid hormone in the blood.
21. CONCLUSIO
NS
Apoptosis is a form of programmed cell death, or “cellular suicide"
(different from necrosis, in which cells die due to injury).
Apoptosis is an orderly process in which the cell’s contents break down
and are packaged into small packets of membrane for “garbage
collection” by immune cells (contrasting with necrosis in which the dying
cell’s contents spill out and cause inflammation).
Apoptosis removes cells during development. It also eliminates pre-
cancerous and virus-infected cells. Apoptosis maintains the balance of
cells in the human body and is particularly important in the immune
system.
