Apoptosis

APOPTOSIS
Pre by lect: Soanb Khattak

MLT UOH
Lecture objective
• At the end of this lecture the student will be able to know
• Apoptosis
• Example of apoptosis
• Morphological changes of apoptosis
• Biochemical changes of apoptosis
• Pathways of apoptosis
• Mechanism of apoptosis
Apoptosis
Its designation „apoptosis“- it is a word from Greek language, which originally
refers to falling of leaves from trees in the autumn.
Apoptosis means the cell kill it's self(suicide).
“programmed cell death.” (embryology)
Apoptosis is an energy dependent programmed cell death for removal of
unwanted individual cells
They kill their own cell activation of enzyme caspase , destruct the membrane
and organelles.
Cell membrane remain intact.
Continue…
• Apoptosis is a pathway of cell death induced by tightly regulated intracellular
program in which cell distend to die activate enzymes that degraded cells own
DNA and nuclear and cytoplasmic protein.
• Apoptosis occur normally both during development and thorough adulthood ,
and serve to remove unwanted, aged and harmful cells.
• Physiological apoptosis
• Pathological apoptosis
Physiological apoptosis
The resorption of the tadpole tail in frog .
Prostrate atrophy after castration.
The formation of the fingers and toes of the fetus requires the removal,
by apoptosis.
Regression of lactating breast after weaning.
When the neutrophil and lymphocytes done their job.
The endometrial cell breakdown during the menstrual cycle.
Pathological apoptosis
DNA damage - Radiation, cytotoxic anticancer drugs, and hypoxia can damage DNA
Accumulation of misfolded proteins. Improperly folded proteins may arise because of
mutations. Excessive accumulation of these proteins in the ER leads to a condition called ER
stress
Cell death in certain infections: Particularly viral infections. An important host response
to viruses consists of cytotoxic T lymphocytes, which induce apoptosis of infected cells
Pathologic atrophy in parenchymal organs after duct obstruction: such as occurs
in the pancreas, parotid gland, and kidney
Morphological changes of apoptosis
• Shrinkage of the cell size, cytoplasm become more dense and organelle tightly
packed.
• Chromatin condensation or aggregation.
• Formation of apoptotic bodies.
• The apoptotic bodies have dense cytoplasm , dense packed organelles with or
without nucleus.
• Phagocytosis occur by macrophages
• This processes occur very rapidly.
• No inflammation processes
Biochemical feature of apoptosis
• Protein cleavage( due to caspase , one type of protease of cysteine

group , some vital protein and destruction of cytoskeleton and
nuclear scaffold)
• DNA breakdown( agarose gel electroporesis , ladder like structure)
• Phagocytic recognition ( release some molecule for recognition
like phophatidylserine, thrombospondin adhesive glycoprotein )
Mechanisms of Apoptosis
The fundamental events in apoptosis is the activation of enzymes called

CASPASES
Caspases are central initiators and executioners of apoptosis
• Cysteine proteases
• Cysteine-dependent
Caspases ASPartate-specific
proteASES
Two distinct pathways converge on caspase activation
Mitochondrial pathway
• Intrinsic pathway
The death receptor pathway
• Extrinsic pathway
Extrinsic pathway (The death receptor pathway)
• FAS and the TNF receptor are integral membrane proteins with
their receptor domains exposed at the surface of the cell
• Binding of the complementary death
activator (FasL and TNF respectively) transmits
• a signal to the cytoplasm
• Activation of caspase 8
• cascade of caspase activation
• Apoptosis
Intrinsic pathway (mitochondrial pathway)
Oxidative damage from free radicals, Radiation, Virus infection,
Nutrient deprivation, Pro-apoptotic Factors
Damage to the mitochondrial membrane increasing permeability
Entry of Cytochrome C into the cytoplasm
Cytochrome C binds to Apaf-1 forming an apoptosome
Apoptosome activates procaspase-9 to caspase-9
Caspase-9 cleaves and activates caspase-3 and caspase-6.
This executioner caspases activate by caspase 3 and cappase 6 a cascade of

proteolytic activity that leads to: Chromatin condensation, DNA fragmentation,
Protein cleavage, Membrane permeability
sclero dinesh
The two pathway of apoptosis differ in their induction and regulation, and both
culminate in the activation of caspases. In the mitochondrial pathway , protein
of the Bcl-2 family , which regulate mitochondrial permeability , become
imbalanced and leakage of various substances from mitochondria lead to
caspase activation. In death receptor pathway signals from plasma membrane
receptors lead to the assembly of adaptor proteins into a death inducing
signaling complex which activates caspases and the end result is the same.
Mitochondria
contain several
proteins
that are capable of
inducing apoptosis
The choice between

cell survival and
death is determined
by the permeability
of mitochondria
Mitochondrial pathway
Mitochondria
BAX Cytochrome c release BCL-2

BAK BCL-XL
BOK BCL-W
BCL-Xs Pro-caspase 9 cleavage MCL1
BAD BFL1
BID DIVA
B IK NR-13
BIM Pro-execution caspase (3) cleavage Several
NIP3 viral
BNIP3 proteins
Caspase (3) cleavage of cellular proteins,

Nuclease activation,
Etc.
Death
• Extrinsic
pathway
THANK YOU

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APOPTOSIS

Pre by lect: Soanb Khattak

DNA and nuclear and cytoplasmic protein.

• Apoptosis occur normally both during development and thorough adulthood ,

and serve to remove unwanted, aged and harmful cells.

• Protein cleavage( due to caspase , one type of protease of cysteine

The fundamental events in apoptosis is the activation of enzymes called

Caspases are central initiators and executioners of apoptosis

The death receptor pathway

Damage to the mitochondrial membrane increasing permeability

Entry of Cytochrome C into the cytoplasm

Cytochrome C binds to Apaf-1 forming an apoptosome

Apoptosome activates procaspase-9 to caspase-9

Caspase-9 cleaves and activates caspase-3 and caspase-6.

This executioner caspases activate by caspase 3 and cappase 6 a cascade of

The choice between

BAX Cytochrome c release BCL-2

Caspase (3) cleavage of cellular proteins,

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