1. Apoptosis is a tightly regulated process of programmed cell death that removes unwanted or damaged cells. It involves activation of caspases and degradation of nuclear DNA and proteins.
2. There are two main pathways that initiate apoptosis - the extrinsic pathway which involves death receptors, and the intrinsic pathway which involves the mitochondria. Both pathways activate caspases that execute the cell death program.
3. Disorders of apoptosis can result in disease states like cancer if cells fail to undergo apoptosis in response to damage, or neurodegeneration if excessive apoptosis occurs. A delicate balance of pro-apoptotic and anti-apoptotic proteins regulates apoptosis.
Content-
1. Background
2. Introduction
3. Difference between apoptosis and necrosis
4. Apoptosis in biologic processes
5. Apoptosis in pathologic processes
6. Morphologic features
7. Techniques to identify and count apoptotic cells
8. Biochemical changes
9. Molecular mechanism of apoptosis
10. Recent advancement and emerging trends in apoptosis
11. References
Content-
1. Background
2. Introduction
3. Difference between apoptosis and necrosis
4. Apoptosis in biologic processes
5. Apoptosis in pathologic processes
6. Morphologic features
7. Techniques to identify and count apoptotic cells
8. Biochemical changes
9. Molecular mechanism of apoptosis
10. Recent advancement and emerging trends in apoptosis
11. References
Apoptosis also known as cell suicide. Difference between necrosis and apoptosis. Changes in apoptosis. Mechanism of apoptosis. Functional significance of apoptosis. Applied aspects of apoptosis
Introduction
Definition
History
Evolution and origin of apoptosis
Significance
Purpose of apoptosis
Steps /process
Morphological and biochemical changes
Mechanism of apoptosis
Caspases
Regulation of apoptosis
Disorders of apoptosis
Application
Conclusion
Referances
Apoptosis also known as cell suicide. Difference between necrosis and apoptosis. Changes in apoptosis. Mechanism of apoptosis. Functional significance of apoptosis. Applied aspects of apoptosis
Introduction
Definition
History
Evolution and origin of apoptosis
Significance
Purpose of apoptosis
Steps /process
Morphological and biochemical changes
Mechanism of apoptosis
Caspases
Regulation of apoptosis
Disorders of apoptosis
Application
Conclusion
Referances
Apoptosis is a
-pathway of cell death that is
-induced by an internally regulated program
-in which cells destined to die activate intrinsic enzymes that --degrade the cells’ own nuclear DNA and also nuclear and cytoplasmic proteins
-With minimal host reaction.
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4. Apoptosis - Definition
A pathway of cell death induced by a tightly
regulated suicidal program, in which the cells
destined to die activate enzymes that degrade
cells own nuclear DNA and nuclear,
cytoplasmic proteins.
5. Significance of apoptosis
• During development → many cells produced
in excess → programmed cell death →
contribute to sculpturing of organs & tissues.
• In human body about one lakh cells are
produced every second by mitosis and a
similar number die by apoptosis.
7. Physiological apoptosis
Programmed cell death is as
needed for proper normal
development as mitosis is.
Examples:
• Formation of fingers & toes of
fetus requires removal by
apoptosis
• Sloughing off of endometrium at
the start of menstruation.
8. Apoptosis in physiologic situations
Programmed destruction during embryogenesis
Involution of hormone dependent tissues
Cell loss in proliferating cell populations
Elimination of harmful self- reactive lymphocytes
Death of host cells
10. Apoptosis: importance in adults
Tissue remodeling (eliminates cells no longer needed):
Virgin mammary gland Late pregnancy, lactation Involution
(non-pregnant, non-lactating)
Apoptosis
Apoptosis
- Testosterone
Prostate gland
11. Apoptosis: in immunity
Immunity (eliminates dangerous cells):
Self antigen
recognizing cell
Organ size (eliminates excess cells):
12. Apoptosis in pathological conditions
- DNA damage
- Accumulation of misfolded proteins
- Cell death in certain infections
- Pathological atrophy in parenchymal organs
17. STAGES OF CLASSIC APOPTOSIS
Healthy cell
DEATH SIGNAL / STIMULI (extrinsic or intrinsic)
Commitment to die (reversible)
EXECUTION (irreversible)
Dead cell (condensed, crosslinked)
ENGULFMENT (macrophages, neighboring cells)
DEGRADATION
18.
19. Initiation of apoptosis by activation of
signalling pathways :
There are two main signalling pathways in apoptosis :
(A) Extrinsic/death receptor-initiated pathway :
28. REGULATION OF
APOPTOSIS
• Release of mitochondrial pro-apoptotic
proteins tightly controlled by BCL2 family of
proteins.
• Antiapoptotic proteins : BCL2, BCLXL & MCL1
• Proapoptotic proteins : BAX and BAK
• BCL2 sensor proteins : BAD, BIM, BID, Puma, Noxa
(also called BH3 proteins)
• Also, cytoplasm of normal cells contains
inhibitors of apoptosis (IAP) which are
neutralized by proapoptotic factors.
31. Apoptosis: Role in Disease
TOO MUCH: Tissue atrophy
TOO LITTLE: Hyperplasia
Neurodegeneration
Thin skin
etc
Cancer
Athersclerosis
etc
32. Neurodegeneration
→Neurons are post-mitotic.
→Neuronal death caused by loss of proper
connections, loss of proper growth factors (e.g.
NGF), and/or damage (especially oxidative
damage).
→Neuronal dysfunction or damage results in loss of
synapses or loss of cell bodies (synaptosis, can be
reversible; apoptosis, irreversible)
→PARKINSON'S DISEASE
→ALZHEIMER'S DISEASE
→HUNTINGTON'S DISEASE etc.
33.
34. CANCER
Apoptosis eliminates damaged cells
(damage => mutations => cancer)
Tumor suppressor p53 controls senescence and
apoptosis responses to damage.
Most cancer cells are defective in apoptotic
response(damaged, mutant cells survive)
High levels of anti-apoptotic proteins
or
Low levels of pro-apoptotic proteins ===>
CANCER
35. CANCER
VIRUS ASSOCIATED CANCER
• Human papilloma viruses (HPV)
•causes cervical cancer
•produces a protein (E6)-binds & inactivates apoptosis promoter p53.
• Epstein-Barr Virus (EBV)
- cause of mononucleosis and a/w some lymphomas
–produces a protein similar to Bcl-2
–produces another protein that causes the cell to
increase its own production of Bcl-2. Both these actions
make the cell more resistant to apoptosis (thus enabling
a cancer cell to continue to proliferate).
36. • Some B-cell leukemia and lymphomas express high
levels of Bcl-2 → block apoptotic signals. The high
levels result from a translocation of BCL-2 gene into
an enhancer region for antibody production.
• Melanoma cells avoid apoptosis by inhibiting
expression of the gene encoding Apaf-1.
CANCER