Apoptosis

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Apoptosis

Published in: Health & Medicine, Technology

Apoptosis

  1. 1. By Michael A. Medez
  2. 2. APOPTOSIS• First described by Carl Vogt in 1842• 1965, distinguished from necrosis• Greek word “falling off”• Programmed Cell Death• Biochemical reactions lead to cell changes and death• Around 50 to 70 billion cells die each day due to apoptosis
  3. 3. APOPTOSIS vs NECROSIS• Apoptosis • Necrosis  Natural Cell Death  Traumatic Cell Death  Stimulated by cell signals  Stimulated by factors  Beneficial external to the cells  Produces cell fragments that  Fatal are able to send signals that  Cannot send signals, leads to facilitate phagocytosis build up of dead tissue and cell debris
  4. 4. PROCESS• Controlled by a diverse range of cell signals  Extracellular (Extrinsic Inducers) • Toxins, hormones, cytokines • Positive Induction or Negative Induction  Intracellular (Intrinsic Inducers) • Initiates in response to stress (heat, radiation, hypoxia, nutrient deprivation)
  5. 5. REGULATION• Mitochondrial Regulation  Mitochondria is essential to cell life  Exploited by apoptotic pathways  Cause mitochondrial swelling or may increase the permeability of the membrane• Direct Signal Transduction  TNF (Tumor Necrotic Factor) Pathway  Fas Pathway
  6. 6. TNF and Fas TNF Pathway • Fas Pathway  TNF is a cytokine produced  Binds the Fas Ligand by macrophages  Formation of Death  Major extrinsic mediator of Inducing Signaling Complex apoptosis (DISC)  Leads to caspase activation  Caspase activation via the via membrane proteins FADD TRADD and FADD  Indirectly leads to activation of transcription factors involved in cell survival and inflammatory response
  7. 7. COMPONENTS• Following activation of TNF and Fas, a balance between proapoptotic and anti-apoptotic members of the Bcl-2 family is established• Proportion of proapoptotic homodimers that form in the outer membrane of the mitochondria, required to make the membrane permeable for the release of caspase activators
  8. 8. CASPASES• Cysteine-dependent aspartate-secific proteases• Play a central role in transduction of apoptopic signals• Highly conserved proteins• Intiator Caspases  Activates by binding to specific oligomeric adaptor protein• Effector Caspases  Activated by active initiator caspases through proteolytic cleavage  Degrade intracellular proteins to carry out cell death program
  9. 9. MECHANISM1. Cell receives stimulus2. Shrinks (breakdown of cytoskeleton)3. Dense cytoplasm, packing of organelles4. Condensation of chromatin (PYKNOSIS)5. Fragmentation of DNA, breaking of nucleus6. Formation of blebs7. Cell breaks, formation of apoptotic bodies8. Phagocytosis
  10. 10. REMOVAL OF DEAD CELLS• Efferocytosis• Dying cells display phagocytotic molecules, phosphatidylserine• Mark the cell for phagocytosis
  11. 11. DEFECTS in APOPTOSIS• p53  Tumor suppressor protein  Accumulates when DNA is damaged  Prevents the cell fro replicating to give it time to repair  Induce apoptosis if damage is extensive and repair efforts fail  Any disruption to its regulation results in impaired apoptosis and possible formation of tumors
  12. 12. INHIBITION and HYPERACTIVITY• INHIBITION • HYPERACTIVITY  Decrease in cell  Loss of control of cell death death  Most common is  HIV CANCER

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