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

1. By
KAUSHAL KUMAR SAHU
Assistant Professor (Ad Hoc)
Department of Biotechnology
Govt. Digvijay Autonomous P. G. College
Raj-Nandgaon ( C. G. )

2. Contents
 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

3. INTRODUCTION
 The word apoptosis comes from the
ancient Greek meaning the;
 “Falling of petals from a flower or of leaves
from a tree in autumn”
 Apoptosis is the process of
programmed cell death.
 Biochemical events lead to characterisitic
cell changes include, cell shrinking,
nuclear fragmentation, chromatin
condensation, and chromosomal DNA
fragmentation.
 Between 50-70 billion cells die each day
due to apoptosis in the average human
adult. For an average child between the
ages of 8-14, approximately 20 billion to 20
billion cells die a day.

5. HISTORY
 German scientist Carl Vogt was first to
describe the principle of apoptosis in
1842.
 In 1972 Kerr first introduced the term
apoptosis in a publication.
 Kerr received the Paul Ehrlich and
Ludwig Darmstaedter prize on march 14,
2000, for his description of apoptosis.
 The 2002 Nobel prize in medicine was
awarded to Sydney Brenner, Horvitz and
john e. Sulston for their work identifying
genes that control apoptosis.

6. 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 cytoplasmic protein.
 It is programed by genetics protocol of program
(control of enzyme, cell membrane, cytoplasmic
molecules, signal transduction ) etc..

7. Evolution of the origin of programmed cell
death
 Mitochondria retain their collection of molecules that can
trigger cell suicide after they enter and stabilize in the
eukaryotic cell.
 This process has evolved to occur only when programmed.

8. SIGNIFICANCE
 In the human body about 100,000 cells are
produced every second by mitosis and a
similar number die by apoptosis(Vaux and
Korsmeyer, 1999,Cell).
1] Development & morphology
 Massive cell death occurs during early
development of the nervous system (>
50percent of all neurons die)
2] Homeostasis
3] Deletion of damaged and dangerous cells

9. Purpose of apoptosis
why should a cell commit suicide
 It’s essential for the proper development and
to maintain homeostasis for the organism.
Apoptosis is needed for proper
development;
 The resorption of the tadpole tail.
 The formation of the fingers and toes of the
fetus.
 The sloughing off of the inner lining of the
uterus.
 The formation of the proper connection
between neurons in the brain.
Apoptosis is needed for self defance
 Cells infected with viruses
 Cells of the immune system cells with DNA
damage
 Cancer cells

10. STEPS
Apoptosis consists of 4 steps:
 the decision to activate the pathway;
 the actually "suicide" of the cell;
 engulfment of the cell remains by
specialized immune cells called
phagocytes;
 degradation of engulfed cell.
 The actual steps in cell death
require:
 condensing of the cell nucleus and
breaking it into pieces
 condensing and fragmenting of
cytoplasm into membrane bound
apoptotic bodies; and
 breaking chromosomes into fragments
containing multiple number of
nucleosomes (a nucleosome ladder)

11. Morphological and biochemical
changes
Classic change Biochemical changes
 Cell shrinkage
 Nuclear fragmentation
 Chromatin condensation
 Chromosomal DNA
fragmentation
 Formation of cytoplasmic
blebs and apoptosis bodies
 Phagocytosis
 Activation of caspases
 Protolysis of cytoskeletal
protein
 Cross linkage of protein
molecules
 Fragmentation of nuclear
chromatin by activation of
nuclease.
 Membrane alteration and
recognition by phagocytosis.

13. Mechanism of apoptosis
extrinsic pathway- cytochrome c caspases cell
death.
A] External signalling pathway
 Apoptosis is triggered by external (extracellular) stimulus.
 Also known as Receptor mediated apoptosis

15. 2] Intrinsic signalling pathway
Intrensic pathway- death receptor caspases cell death.
 Also called as mitochondria mediated pathway.

16. Caspases- the initiator & executioner of apoptosis
 There are 14 mammalian caspases identified to date.
 The term caspases is derived from cysteine-dependent aspartate-specific proteases
 Caspases subdivided into 3 functional groups : 1. initiator caspases- (caspases 2,8,9,10) 2.
executioner caspases (caspases 3,6,7) 3. inflammatory caspases (1,4,5,11,12)
 Single chain of pro enzymes. Contains an N-terminal domain, a small subunit and a large
subunit (similar to a ribosome).
 Apoptosis stimulus activation substrate cleavage enzyme.
Some common targets
Executioner
caspase
protein kinases Laminins
Proteins of
cytoskeleton
An endonuclease called
caspase activated DNase
(CAD)

17. Regulation of apoptosis
 Regulatory protein – BCL-2, equivalent to CED-9
 Apoptosis depends on binding of BCL-2 with pro
apoptotic and anti apoptotic proteins.
 Situated in the outer mitochondrial membrane.
 Apaf-1 equivalent to CED-4.

18. Disorder of apoptosis
TOO MUCH- tissue atrophy
- Neurodegeneration , thin skin etc.
TOO LITTLE- hyperplasia
- cancer, athersclerosis etc.
Apoptosis inhibition
 Neoplastic disease
 Autoimmunity [ e.g. systemic lupus
erythematosus]
 Viral infection
Hyperactive apoptosis
 Neurodegenerative disease

19. Importance of apoptosis
1. Crucial for embryonic development;
- Errors in apoptosis can lead birth defects.
2. Importance for maintaining homeostasis;
- Cell death is balanced with mitosis to regulate cell
number.
3. Apoptosis helps eliminates cells that are
injured;
- Such injured cells include;
- A) cells with damaged DNA.
- B) cells with misfolded proteins
- C) cells suffering from certain infections etc.
4. Important in normal physiology/development
- DEVELOPMENT; immune systems maturation,
morphogenesis, neural development.
- Adult ; immune privilege, DNA damage and wound
repair.

20. Conclusion
 Apoptosis play a significant role in survival by
maintaining homoeostasis in multicellular organisms
and the management of many diseases.
 Evidence show that malfunctioning of apoptosis
pathway may cause several human diseases like
cancer, neurodegenerative as well as several type of
autoimmune disorder.

21. References
BOOKS
 The Cell- A molecular approach 4th edition- G.M. Cooper & R.E. Hausman
 Cell and molecular biology 6th edition- Gerald Karp.
Articles
 Apoptosis—an introduction by Alfons Lawen 25:888–896, 2003.
 Apoptosis – reprogramming cell fate. Hoi Hung Cheung et al- Volume 2012,
Article ID 685852, 8 pages.
 Apoptosis and disease- R. Ramírez Chamond et al - Vol. 14, No. 6, pp. 367-
374
 Introduction to Apoptosis - by Andreas Gewies in 2003, pp. 1-26