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Apoptosis
BY
Robin Singh
B.Sc (hons) Biochemistry
Contents
• Introduction
• Impotrance of Apoptosis
• Mechanism
• Extrinsic Pathway
• Intrinsic Pathway
• Apoptosis related Disorders
Definition:
• the death of cells which occurs as a normal and controlled part of an
organism's growth or development.
(Wikipedia)
• Cells die when they fail to receive life maintaining signals or when
they receive a death signal, such programmed death of cell is called
Apoptosis.
(Lodish et al. ; 2004)
• Cell death may occur due to
• Accident or damage due to traumatic event.
• Death by suicide.
• Suicidal death also occurs in two ways, i.e. Apoptosis and Necrosis.
Importance
• helps to shape organs and carve out the interdigital webs of the
fingers and toes.
• Both the nervous system and the immune system arise through
overproduction of cells followed by the apoptotic death
• Resorption of tail in
tadpole
• Shedding off of
endometrium in the
process of
menstruation
• Useful for killing virus infected cells.
• Killing cancer cells.
• Killing DNA damaged cells.
Mechanism
Extrinsic Pathway
• Extrinsic pathway is initiated by external signal.
• Most common extrinsic factor for initiation is TNF(alpha) secrete by T-killer
cells.
• Killler lymphocyte attaches to death receptor’s of the diseased cell through
Fas ligands or TNF.
• The FADD adaptor protein is attached to death receptor (in cytoplasm).
• Eventually inactivated procaspase-8 or 10 attaches to FADD to activate
itself.
• Activated caspase-8 breaks other proteins and actin cytoskeleton bringing
the death for cell.
Intrinsic Pathway
• Most of the times intrinsic pathway is initiated due to damage of DNA
in the cell.
• DNA lesions leads to the activation of ATM which activates tumor
suppressor p53 protein.
• p53 activates protein BAX which form pores on outer mitochondrial
membrane.
• This leads to leakage of calcium ion, hydrogen ions along with protein
cytochrome – c.
• Cytochrome C forms ‘Apoptosome’ by attaching to adaptor protein.
• Apoptosome activates Caspases especially caspase-9 which cleaves
other protein and activates other caspases continuing the cycle.
• Caspase also cleaves the actin cytoskeleton, causing shrinkage of the
cell and its death.
Apoptosis related Disorders
• Neurodegenerative diseases such as Alzheimer's disease, Parkinson's
disease, and amyotrophic lateral sclerosis.
• Ischaemic injury after myocardial infarction, stroke, and reperfusion.
• Autoimmune diseases such as hepatitis and graft versus host.
• Decreased or inhibited apoptosis is a feature of many malignancies,
autoimmune disorders such as systemic lupus erythematosus, and
some viral infections.
• The role of apoptosis in cancer has probably received the greatest
research effort.
• Increased apoptosis is characteristic of AIDS
END

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Apoptosis

  • 2. Contents • Introduction • Impotrance of Apoptosis • Mechanism • Extrinsic Pathway • Intrinsic Pathway • Apoptosis related Disorders
  • 3. Definition: • the death of cells which occurs as a normal and controlled part of an organism's growth or development. (Wikipedia) • Cells die when they fail to receive life maintaining signals or when they receive a death signal, such programmed death of cell is called Apoptosis. (Lodish et al. ; 2004)
  • 4. • Cell death may occur due to • Accident or damage due to traumatic event. • Death by suicide. • Suicidal death also occurs in two ways, i.e. Apoptosis and Necrosis.
  • 5.
  • 6.
  • 8. • helps to shape organs and carve out the interdigital webs of the fingers and toes. • Both the nervous system and the immune system arise through overproduction of cells followed by the apoptotic death
  • 9. • Resorption of tail in tadpole • Shedding off of endometrium in the process of menstruation
  • 10. • Useful for killing virus infected cells. • Killing cancer cells. • Killing DNA damaged cells.
  • 13. • Extrinsic pathway is initiated by external signal. • Most common extrinsic factor for initiation is TNF(alpha) secrete by T-killer cells. • Killler lymphocyte attaches to death receptor’s of the diseased cell through Fas ligands or TNF. • The FADD adaptor protein is attached to death receptor (in cytoplasm). • Eventually inactivated procaspase-8 or 10 attaches to FADD to activate itself. • Activated caspase-8 breaks other proteins and actin cytoskeleton bringing the death for cell.
  • 15. • Most of the times intrinsic pathway is initiated due to damage of DNA in the cell. • DNA lesions leads to the activation of ATM which activates tumor suppressor p53 protein. • p53 activates protein BAX which form pores on outer mitochondrial membrane. • This leads to leakage of calcium ion, hydrogen ions along with protein cytochrome – c. • Cytochrome C forms ‘Apoptosome’ by attaching to adaptor protein.
  • 16. • Apoptosome activates Caspases especially caspase-9 which cleaves other protein and activates other caspases continuing the cycle. • Caspase also cleaves the actin cytoskeleton, causing shrinkage of the cell and its death.
  • 18. • Neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. • Ischaemic injury after myocardial infarction, stroke, and reperfusion. • Autoimmune diseases such as hepatitis and graft versus host. • Decreased or inhibited apoptosis is a feature of many malignancies, autoimmune disorders such as systemic lupus erythematosus, and some viral infections. • The role of apoptosis in cancer has probably received the greatest research effort. • Increased apoptosis is characteristic of AIDS
  • 19. END