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Apopotosis why and how ?
1. Why and How?
Presented By – Gyanendra Kumar Prajapati
1st year M.Pharm
Guided By – Mr.G.S.Prasanna
KLE University’s College of Pharmacy,
Bengaluru
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2. 1. Definition
2. Causes of apoptosis : Physiological and pathological
Conditions
3. Mechanism of apoptosis
4. Pathways of apoptosis
5. Examples of Apoptosis
6. Reference
3. Apoptosis is a pathway of cell death in which cells
activate enzymes that degrade the cells and its
organelles.
Plasma membrane remains intact - structure is altered
>>> Subsequently apoptotic cell becomes target for
phagocytosis.
4. • Initially recognized in 1972
•Greek designation for “falling off”
•Eliminate potentially harmful cells
•Pathologic event when cells are damaged beyond
repairs, especially when the damage affect the cell’s
DNA proteins in these situations.
5. •Death by apoptosis is a normal
phenomenon that serves to eliminate cells
that are no longer needed .
Example :
•The programmed destruction of cells during
embryogenesis.
•Involution of Hormone dependent tissues
•Cell loss in proliferating cell populations
•Cell death induced by cytotoxic
lymphocytes
•Infected and neoplastic cells.
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Apoptosis in bud
formation during
which many
interdigital cells
die. They are stained
black by a TUNEL
method
Incomplete
differentiation in two
toes due to lack of
apoptosis
7. DNA damage
Accumulation of misfolded proteins
Cell injury in certain infections
Pathological atrophy in parenchymal
organs.
8. Cell shrinkage
Chromatin condensation
Nuclear fragmentation
Chromosomal DNA fragmentation
Formation of cytoplasmic blebs& apoptotic bodies
Phagocytosis.
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9. Apoptosis activation of enzyme called
caspases
Caspases depends on a finely turned
balance
b/w production of pro and anti-apoptotic
proteins.
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Mitochondrial pathway+ death receptor
pathway → caspases
12. The Mitochondria (Intrinsic) Pathway of Apoptosis
Mitochondria contain several proteins that are
capable of inducing apoptosis,
Include cytochrome C and other proteins that
neutralize endogenous inhibitors of apoptosis.
Permeability of mitochondria
Damage DNA or accumulate unacceptable
amounts of misfolded proteins
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13. The death receptor (Extrinsic) Pathway of
Apoptosis
Many Cells express surface molecules called
death receptors that trigger apoptosis.
Tumor necrosis factor (TNF) receptor family which
contain in their cytoplasmic regions a conserved
“death domain” so named it mediates interaction
with other proteins in valued in cell death.
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14. The mitochondrial and death receptor pathways
lead to the activation of the initiator caspases,
activated capases cleave numerous targets
activation of nucleases that degrade DNA and
nucleus proteins capses
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15. Cells entire phagocytes by producing “eat – me”
signals
Phosphatidylserine is present on the inner leaflet
of plasma membrane
Apoptotic cells this phospholipids“flips to the outer
leaflet
Tissue macrophoages and leads to phogocytosed
of the apoptosis
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16. Prompt clearance of the dead cells
Secondary membrane damage and release their
cellular content
Dead cells disappear without leaving trace and
inflammation is virtually absent
Emphasize that distinctions between necrosis &
apoptosis these two from of cells death may co
exist.
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17. Cell death in many situations is caused by
apoptosis.
Illustrate the role two pathways of apoptosis in
normal physiology and in disease.
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18. Hormone - sensitive cells deprived of the relevant
hormone
lymphocytes that are not stimulated by antigens
and cytokines that are not stimulated by antigens
and neurons deprived of nerve growth factor die
by apoptosis.
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19. Chemotherapeutic agents induces DNA damage
which is severe may trigger apoptic death
DNA is damage the P53 protein accumulates in
cells
Cell cycle to allows the DNA to be repaired before
it is replicated
Synthesis of pro-apoptotic members of the certain
BCL- 2 family.
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20. Lymphocytes capable of recognizing self antigens
Encounter self antigens the cell die by apoptosis
Failure of apoptosis of self reactive lymphocytes is
one of the causes of autoimmune disease.
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21. Robbins' pathologic basis of disease. R. S. Cotran, V.
Kumar and S. L. Robbins. W. B. Saunders,
Philadelphia, 1989. No. of pages: 1519.
Pharmacology – Rang And Dale of pages: 69
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