Apoptosis | Anatomy2Medicine
Apoptosis Causes

Apoptosis

 

  • Apoptosis
      • programmed cell death. (MCQ)
      • involutional process is similar to the physiologic loss of leaves from a tree; apoptosis is a Greek term for “falling away from.”
      • Examples of apoptotic removal of cells
        • irreparable DNA damage (from free radicals, viruses, cytotoxic immune mechanisms),
        • protection against neoplastic transformation. (MCQ)
        • It is an important mechanism for
        • physiologic cell removal during embryogenesis (MCQ)
        • programmed cell cycling (e.g., endometrial cells during menstruation). (MCQ)
      • Morphologic features
        • A tendency to involve single isolated cells or small clusters of cells within a tissue
  • Progression through a series of changes marked by a lack of inflammatory response
  • Blebbing of plasma membrane(MCQ)
  • cytoplasmic shrinkage
  • chromatin condensation
  • Budding of cell
          • separation of apoptotic bodies (membrane-bound segments) (MCQ)
          • Phagocytosis of apoptotic bodies
  • Councilman bodies in viral hepatitis(MCQ)
          • Involution and shrinkage of affected cells and cell fragments, results in small round eosinophilic masses often containing chromatin remnants,
  • Necrosis vs Apoptosis in Morphologic features
          • Gross irreversible cellular injury
          • Involves many contiguous cells
          • Increased cytoplasmic eosinophilia due to denaturation of proteins
          • Progressive nuclear condensation and fragmentation with eventual disappearance of nuclei
          • Preservation of tissue architecture in early stages of coagulative necrosis
      • Biochemical events
        • injurious stimuli (e.g., free radicals, radiation, toxic substances, withdrawal of growth factors or hormones) trigger a variety of stimuli, including
  • cell surface receptors such as FAS (MCQ)
  • mitochondrial response to stress,
  • cytotoxic T cells.
        • The extrinsic pathway of initiation
          • mediated by cell surface receptors exemplified by FAS, a member of the tumor necrosis factor receptor family of proteins. (MCQ)
          • This pathway is initiated by signaling by molecules such as the FAS ligand which in turn signals a series of events that involve activation of caspases
  • Caspases
            • aspartate-specific cysteine proteases (MCQ)
            • referred to as “major executioners” or “molecular guillotines.” (MCQ)
          • The death signals are conveyed in a proteolytic cascade, through activation of a chain of caspases and other targets.
          • The initial activating caspases are caspase-8 and caspase-9, (MCQ)
          • terminal caspases (executioners) include caspase-3 and caspase-6 (MCQ)
        • The intrinsic, or mitochondrial, pathway
          • is initiated by the loss of stimulation by growth factors
          • results in the inactivation and loss of bcl-2 and other antiapoptotic proteins from the inner mitochondrial membrane(MCQ)
            • This loss results in
              • increased mitochondrial permeability
              • release of cytochrome c(MCQ)
              • stimulation of proapoptotic proteins such as bax and bak(MCQ)
          • Cytochrome c interacts with Apaf-1 causing self-cleavage and activation of caspase-9(MCQ)
          • Downstream caspases are activated by upstream proteases and act themselves to cleave cellular targets.
        • Cytotoxic T-cell activation
          • characterized by direct activation of caspases by granzyme B
  • granzyme B (MCQ)
            • is a cytotoxic T-cell protease
            • it directly activates the caspase cascade.
  • The entry of granzyme B into target cells is mediated by perforin, a cytotoxic T-cell protein.
        • typical “laddering” appearance of DNA on electrophoresis(MCQ)
          • Degradation of DNA by endonucleases into nucleosomal chromatin fragments that are multiples of 180–200 base pairs results in the typical “laddering” appearance of DNA on electrophoresis.
          • This phenomenon is characteristic of, but not entirely specific for, apoptosis.
        • Activation of transglutaminases crosslinks apoptotic cytoplasmic proteins.
  • TUNEL assay (MCQ)
        • Terminal Transferase dUTP Nick End Labeling (MCQ)
        • A way to quantitate cleaving of nucleosomes and, thus, apoptosis.
      • Caspase assays are used as apoptotic markers(MCQ)
      • Genes that regulate apoptosis
  • bcl-2 (MCQ)
          • gene product inhibits apoptosis
  • bax (MCQ)
          • gene product facilitates apoptosis
  • p53 gene product(MCQ)
          • decreases transcription of bcl-2
          • increases transcription of bax
          • facilitates apoptosis
  • Necrosis vs Apoptosis in Biochemical features
        • Passive form of cell death
        • does not require gene involvement or new protein synthesis
        • DNA fragmentation is haphazard rather than regular, resulting in an electrophoretic smudge pattern
        • Marked inflammatory reaction
        • There is liberation of lysosomal enzymes digestion of cell membranes
        • disruption of cells I
        • nflux of macrophages due to release of chemotactic factors
  • Removal of debris by phagocytic macrophages