APOPTOSIS

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APOPTOSIS

• Programmed Cell Death And Its Role In Development

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apoptosis

• From classical Greek, it means falling off, as
  in the falling off of petals from a flower or
  leaves from a tree.

WHY?
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Apoptosis (a-po-TOE-sis)

• Apoptosis (also known as Programmed Cell Death
  (PCD) or Cell Suicide) is a genetically
  prescribed series of events leading to the death
  of a cell and its rapid phagocytosis (uptake) by
  surrounding scavenger cells.

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The Death Of A Cell

• NECROSIS
• Caused by cellular trauma or injury
• Results in swelling/ lysis of cell and release of
  cell contents into surrounding environment
• Causes inflammation and (potentially) autoimmune
  response

• APOPTOSIS
• Triggered as a controlled response
• Results in compaction of cell and
  compartmentalization of cellular contents into
  blebs
• Avoids inflammation associated with necrosis

Bad Death
Good Death
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Apoptosis - History

• Most of the characteristics had been described
  by the early 50s, but the scientific community
  didnt really begin to appreciate its
  significance until 1972.

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Apoptosis in Scientific Literature
Number of MedLine Citations
Year
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Fields Impacted By The Study Of Apoptosis

• Developmental Biology
• Immunology
• Cell Biology
• Neuroscience
• Cancer Biology
• Plant Biology

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Morphological Characteristics

• Nuclear compaction
• Cytoplasmic condensation
• Breakdown of nucleus into discrete fragments
• Cell breakdown into membrane-bound apoptotic
  bodies (blebs) containing intact organelles

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Biochemical Characteristics

• Upregulation of endonuclease
• Cleavage of DNA into 200 bp fragments

• Mitochondrial release of Cytochrome C
• Activation of caspase (cysteine-aspartic acid
  protease) enzymes

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Stimuli Which Trigger Apoptosis

• Withdrawal of growth factors
• Irradiation (gamma, U.V.)
• Heat-shock/cold-shock
• Steroid treatment
• Treatment with chemotherapeutic agents
• Engagement of death receptors

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Diseases Associated With Apoptosis

• Excess/Inappropriate Apoptosis
• AIDS
• Neurodegenerative Disorders
• Alzheimers Disease
• Parkinsons Disease
• ALS (Lou Gehrigs Disease)
• Ischemic Injury
• Myocardial Infarction
• Stroke
• Toxin-induced liver disease
• Alcohol

• Defective Apoptosis
• Cancer
• Follicular Lymphomas
• Hormone-dependent tumors
• Breast Cancer
• Prostate Cancer
• Ovarian Cancer
• Autoimmune Disorders
• Systemic Lupus Erythematosus
• Glomerulonephritis

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Apoptosis In Development

• Removal of inter-digital webbing/separation of
  digits
• Resorption of the tadpole tail at the time of its
  metamorphosis into a frog
• Elimination of autoreactive lymphocytes during
  development of the immune system
• Formation of synapses between neurons in the brain

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Apoptosis In Development
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The pattern of cell death is determined by the
mesoderm.
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Genetic Control of Apoptosis In Development
Caenorhabditis elegans
The fates of each and every cell during
development to the adult are known (Sulston et
al., 1983). Thus, cell fate studies can be done
very precisely.
The adult hermaphrodite C. elegans forms 1090
somatic cells, of which 131 die by apoptosis.
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Cell death in the nematode is under genetic
control.
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apoptosis (a-po-TOE-sis)

• From classical Greek, it means falling off, as
  in the falling off of petals from a flower or
  leaves from a tree.

WHY?
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For More Information.
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(Course Information ? Readings ? Reading 11)
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