Apoptosis, program cell death

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

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

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.

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.

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..

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.

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

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

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)

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.

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

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

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)

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.

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

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.

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.

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

Apoptosis, program cell death

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