Apoptosis

1. PROGRAMMED CELL DEATH
(APOPTOSIS )
by
Dr. Naushi Mujeeb
professor, Dept of physiology

2. • Introduction:
•
– Apoptosis is a naturally occurring
process by which a cell is directed
to programmed cell death.
• – The name Apoptosis is a Greek
name describing falling of leaves.
• – The course apoptosis is
accompanied by characteristic
changes in the cell morphology.
• Apoptosis is genetically
programmed cell death which
leads to tidy breakdown and
disposal of cells.

3. • Morphologically,
apoptosis is characterized by
changes in the cell membrane
(with formation of small blebs
known as apoptotic bodies,
shrinking of nucleus, chromatin
condensation, and
fragmentation of DNA.
• Macrophages and other
phagocytic cells recognize
apoptotic cells and remove
them by phagocytosis without
inflammatory phenomena
developing.

5. • There are many observable morphological and biochemical
differences between necrosis and apoptosis:
 Morphological features
Necrotic cells Apoptotic cells
Volume enlargement  Volume reduction
 Swelling of cytoplasm  Shrinking of cytoplasm
& mitochondria  No loss of membrane integrity
 Loss of membrane integrity
 No vesicle formation  Formation of apoptotic bodies
 Condensation of chromatin &
DNA fragmentation

6. • ◘ Basic function of Apoptosis-
•
1- Tissue Homeostasis.
2- Development and Differentiation.
3- Immune System.
4- Cell Damage.

7. • 1- Tissue Homeostasis.

8. • 2- Development and Differentiation –
• • Apoptosis has an indispensable role in development and differentiation
processes especially in the embryo.
• • Here, it provides a means to switch off cells no longer needed during
embryonal morphogenesis and synaptogenesis .

9. Apoptosis is a beneficial and important phenomenon:
 In embryo
1. During embryonic development, help to digit formation.
• Lack of apoptosis in humans
can lead to webbed fingers
called “ syndactyly ”.

10. • 3- Immune System-
• • In the immune system, apoptotic programs are activated in
various situations.
• • Examples include:
• 1– Elimination of target cells (e.g., virus-infected cells) by
cytotoxic T lymphocytes.
• 2– Elimination of auto-reactive B- or T-lymphocytes, natural
selection and elimination of cells in the thymus: 95% of T cells
that migrate to the thymus are eliminated by apoptosis.

11. • 4- Cell Damage-

12. • 4- Cell Damage-
• At the center of the apoptotic
program is a family of proteases
named Caspases.
• They are involved in the initiation
and execution of the program and
can be activated by a large number
of stimuli via two central pathways,
one involving mitochondria, the
other using trans-membrane
receptors of the tumor necrosis
factor α (TNF α) class.

13. Cell death can occur via several processes (about 11 type):
1. Apoptosis
2. Necrosis
3. Autophagy
4. Entosis
5. Oncosis
6. Pyroptosis
.
.
.
11.

14. • Apoptosis is the physiological cell death which unwanted or
useless cells are eliminated during development and other
normal biological processes.
• Necrosis is the pathological cell death which occurs when cells
are exposed to a serious physical or chemical insult (hypoxia,
hyperthermia, ischemia).

15. The major pathways of apoptosis –
1. The intrinsic pathway:
- Activation of apoptosis via mitochondria is an intrinsic pathway.
2. The extrinsic pathway –
- using trans-membrane receptors of the tumor necrosis factor α (TNF α)
class

16. • Cancer and apoptosis –
• The importance of apoptotic pathway in cancer progression is seen when there
are mutations that alter the cell ability to undergo apoptosis and allow
transformed cell to keep proliferation rather than die.
• Such genetic alterations include translocation of Bcl-2 gene in lymphomas that
prevents apoptosis and promotes resistance to cytotoxic drugs.
• The Family of Bcl-2 Proteins are known as gatekeepers of Apoptosis.
• Various oncogene products can suppress apoptosis.

17. • It is clear that a number of anticancer drugs induce apoptosis
in cancer cells.
• The problem is that they usually do this in normal proliferation
cells as well.
• Therefore, the goal should be to manipulate selectively the
genes involved in inducing apoptosis in tumor cells.
• Understanding how genes work may go a long way to
achieving this goal.

18. Aberrant cell death can lead to many human diseases:
 Decreased apoptosis Cancer, Autoimmune disorders
 Excessive apoptosis Neurodegenerative and
immunodeficiency (AIDS) disorders , Ischemia

19. • END