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APOPTOSIS. “Cell Death” By Brian Abadie, Emily Anderson, andJohn Ramsey. Characteristics of Apoptosis. Shrinks Blebbing Nucleus breaks down, breaks into small membrane wrapped fragments Phagocyte signals Apoptosis Video. Importance of Apoptosis. Maturing organisms Virus Immune System

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apoptosis

APOPTOSIS

“Cell Death”

By Brian Abadie, Emily Anderson, andJohn Ramsey

characteristics of apoptosis
Characteristics of Apoptosis
  • Shrinks
  • Blebbing
  • Nucleus breaks down, breaks into small membrane wrapped fragments
  • Phagocyte signals
  • Apoptosis Video
importance of apoptosis
Importance of Apoptosis
  • Maturing organisms
  • Virus
  • Immune System
  • DNA damage
what is a caspase
What is a Caspase?
  • Single chain of pro-enzymes
  • Contains an N-terminal domain, a small subunit and a large subunit (similar to a ribosome)
  • Apoptotic stimulus Activation Substrate Cleavage Enzyme
3 types of caspases
3 Types of Caspases
  • Inflammatory Caspases: -1, -4, and -5
  • Initiator Caspases: -2, -8, -9, and -10
    • Long N-terminal domain
    • Interact with effector caspases
  • Effector Caspases: -3, -6, and -7
    • Little to no N-terminal domain
    • Initiate cell death
two caspase pathways
Two Caspase Pathways

Extrinsic Pathway

Death Ligand

Death Receptors

Caspases

Cell Death

two caspase pathways7
Two Caspase Pathways

Intrinsic Pathway

Mitochondria

Cytochrome C

Apoptosome Complex

Caspases

Cell Death

cancer and apoptosis
Cancer and Apoptosis
  • http://www.youtube.com/watch?v=qjjHKDn12qI
  • Evasion of apoptosis can lead to cancer
treatment options
Treatment Options
  • Activate apoptosis in cancer cells, problem solved.
  • Finding useful mechanisms
  • Needs to be selective
  • Pathways (trail)
  • IAPs
  • Seaweed?
slide11
IAPs
  • Inhibitor of Apoptosis Proteins

Neutralize them or prevent their production

  • Inhibit one part in the cascade = failure to apoptose
  • Smac mimetics
  • Bcl proteins
  • Elevated Bcl

Confers resistance to

chemotherapy

gene expression
Gene Expression
  • Down regulation of XIAP

Most potent endogenous IAP

  • Using Adenovirus vector
  • ShRNA achieves delivery

And long term inhibition