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Understanding Apoptosis Mechanisms

Apoptosis is a regulated mechanism of programmed cell death that eliminates unwanted or damaged cells with minimal host reaction. It involves three main steps: initiation, execution, and recognition/removal of apoptotic bodies, and plays critical roles in both physiological processes, such as embryonic development and tissue involution, and pathological conditions, including cancer and neurodegenerative diseases. The process is initiated through intrinsic (mitochondrial) or extrinsic (death receptor) pathways, leading to cellular degradation and phagocytosis of apoptotic bodies.

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38 views17 pages

Understanding Apoptosis Mechanisms

Apoptosis is a regulated mechanism of programmed cell death that eliminates unwanted or damaged cells with minimal host reaction. It involves three main steps: initiation, execution, and recognition/removal of apoptotic bodies, and plays critical roles in both physiological processes, such as embryonic development and tissue involution, and pathological conditions, including cancer and neurodegenerative diseases. The process is initiated through intrinsic (mitochondrial) or extrinsic (death receptor) pathways, leading to cellular degradation and phagocytosis of apoptotic bodies.

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Rania
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APOPTOSIS

◦ Apoptosis: From a Greek word falling: programmed


cell death
◦ Regulated mechanism of cell death by enzyme
activation that serves to eliminate unwanted and
irreparably damaged cells, with least possible host
reaction
◦ Apoptotic cells break up into fragments, called
apoptotic bodies, which contain portions of the
cytoplasm and nucleus.
Steps
◦1. Initiation
◦2.Execution
◦3.Recognition and Removal of apoptotic body
Role of Apoptosis: Physiological
◦ Organised cell destruction during embryonic
development like removing the web tissue between
the fingers and toes, Regression of duct systems in
sexual development
◦ Involution of cells in hormone dependent tissues e g
endometrial shedding, regression of lactating breast,
prostatic atrophy in old age
◦ Involution of the thymus in early age
◦ Bone remodelling
Role of Apoptosis: Pathological
◦ Removal of Tumour cells exposed to chemotherapeutic agents
◦ Cytotoxic T cells induced cell destruction in immune mechanisms
of transplant rejection
◦ Progressive depletion of CD 4 +T cells in the pathogenesis of AIDS
◦ Cell death in viral infections
◦ Cell death in response to injuries like radiation , hypoxia, thermal
injury
◦ Degenerative diseases of CNS e g Alzheimer’s, Parkinson’s disease
Initiation of Apoptosis- Various stimuli
◦ Loss of survival signals: Involution of hormone dependent tissues
upon hormone withdrawal, certain viral infections
◦ DNA damage: radiation, cytotoxic drugs and hypoxia
◦ Accumulation of misfolded proteins :cystic fibrosis ,Alzheimer’s
disease ,Parkinson’s diseases
Mechanisms of Initiation
i Intrinsic/ mitochondrial pathway
ii extrinsic/ death receptor-initiated pathway
The Intrinsic (Mitochondrial) Pathway

◦Mitochondrial proteins like cytochrome C when


released into the cytoplasm can initiate the
apoptosis
◦Cells contain 2 types of factors that regulate
apoptosis
◦Anti apoptotic or Growth promoting proteins: Bcl2
,Bclx
◦Pro apoptotic or Death promoting proteins: BH 3
◦When apoptotic process is initiated, Pro
apoptotic proteins block the function of Bcl 2
and Bcl x
◦And activate apoptotic mechanism by creating
channels that allow cytochrome c from the
inner mitochondrial membrane to leak out
into the cytoplasm
◦Cytochrome C will stimulate Caspase 9
(Initiator caspase)which starts the actual
process of apoptosis
The Extrinsic (Death Receptor)
Pathway
◦Initiated by activation of death receptors on
cellular membrane
◦Death receptors are mainly members of the TNF
receptor
◦Action of an external stimulus on this membrane
receptor activates initiation by Caspase 8 and 10
(Initiator caspases) stimulation
Execution Phase
◦ Mitochondrial pathway: activation of the initiator caspase 9
◦ Death receptor pathway : activation of initiators caspases 8
and 10
◦ This will result in activation of Executioner caspases viz.
caspase 3 and 6
◦ They will act on many cellular components resulting in
degradation
◦ Activate DNAses which results in degradation of the
nuclear matrix and fragmentation of nuclei
Removal of Dead Cells
◦Apoptotic cells undergo fragmentation to
form apoptotic bodies
◦They are easily get phagocytosed.
◦The dead cells are disappeared completely
Morphological Changes
Morphological Changes
1.Cell shrinkage
2. Chromatin condensation and fragmentation
of nucleus
3. Formation of cytoplasmic blebs and
apoptotic bodies
4.Phagocytosis of apoptotic bodies by
macrophages
References
◦Pathologic basis of disease-Robbins and
Cotran, 9th Edition
◦Medical Physiology for undergraduates-Indu
Khurana, 2nd Edition

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