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NECROPTOSIS
Dr.Jeena Raj
Department of Pathology
What are the two principal types of cell death???
Death of cells occurs mainly in two ways:
1. Necrosis--(irreversible injury) changes produced by
enzymatic digestion of dead cellular elements
2. Apoptosis--vital process that helps eliminate unwanted
cells--an internally programmed series of events effected
by dedicated gene products
Difference between apoptosis and necrosis
Necrosis Apoptosis
Stimuli Hypoxia, Toxins Physiologic and pathologic
conditions
Histologic
appearance
Cell swelling, disruption of
organelles
Single cell, chromatin
condensation, apoptotic bodies
DNA
breakdown
Random and diffuse Internucleosomal
Mechanism ATP depletion membrane injury Gene activation, endonucleases,
proteases
Tissue
reaction
Inflammation No inflammation, phagocytosis of
apoptotic bodies
What is Necroptosis??
• Form of cell death
• Shares aspects of both necrosis and apoptosis
• Also known as Programmed necrosis
• Caspase independent programmed cell death
Characteristics
• Loss of ATP
• Cellular and organelle swelling
• Generation of Reactive oxygen species
• Release of lysosomal enzymes
• Rupture of plasma membrane
• Triggered by signal transduction pathways
Molecular mechanism
• ✅ It involves two kinases called receptor-interacting protein kinase 1 and 3
(RIPK1 and RIPK3).
• ✅ Ligation of TNFR1 recruits these kinases into a multiprotein complex, and
RIPK3 phosphorylates a cytoplasmic protein called MLKL.
• ✅ In response to its phosphorylation--> MLKL monomers
assemble into oligomers
• Translocate from the cytosol to the plasma membrane-->
plasma membrane disruption
• ✅ This explains the morphologic similarity of necroptosis with
necrosis initiated by other injuries
Examples
• Physiologic--> Mammalian bone growth plate
• Pathologic--> Steatohepatitis, Acute pancreatitis,
Parkinson disease, ischemic reperfusion injury
• Host defense against certain viruses like CMV.
Thank you

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NECROSIS AND APOPTOSIS POWERPOINT PRESENTATION

  • 2. What are the two principal types of cell death???
  • 3. Death of cells occurs mainly in two ways: 1. Necrosis--(irreversible injury) changes produced by enzymatic digestion of dead cellular elements 2. Apoptosis--vital process that helps eliminate unwanted cells--an internally programmed series of events effected by dedicated gene products
  • 4. Difference between apoptosis and necrosis Necrosis Apoptosis Stimuli Hypoxia, Toxins Physiologic and pathologic conditions Histologic appearance Cell swelling, disruption of organelles Single cell, chromatin condensation, apoptotic bodies DNA breakdown Random and diffuse Internucleosomal Mechanism ATP depletion membrane injury Gene activation, endonucleases, proteases Tissue reaction Inflammation No inflammation, phagocytosis of apoptotic bodies
  • 5. What is Necroptosis?? • Form of cell death • Shares aspects of both necrosis and apoptosis • Also known as Programmed necrosis • Caspase independent programmed cell death
  • 6. Characteristics • Loss of ATP • Cellular and organelle swelling • Generation of Reactive oxygen species • Release of lysosomal enzymes • Rupture of plasma membrane • Triggered by signal transduction pathways
  • 8. • ✅ It involves two kinases called receptor-interacting protein kinase 1 and 3 (RIPK1 and RIPK3). • ✅ Ligation of TNFR1 recruits these kinases into a multiprotein complex, and RIPK3 phosphorylates a cytoplasmic protein called MLKL.
  • 9. • ✅ In response to its phosphorylation--> MLKL monomers assemble into oligomers • Translocate from the cytosol to the plasma membrane--> plasma membrane disruption • ✅ This explains the morphologic similarity of necroptosis with necrosis initiated by other injuries
  • 10. Examples • Physiologic--> Mammalian bone growth plate • Pathologic--> Steatohepatitis, Acute pancreatitis, Parkinson disease, ischemic reperfusion injury • Host defense against certain viruses like CMV.