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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

“Cell Death”

By Brian Abadie, Emily Anderson, andJohn Ramsey


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Characteristics of Apoptosis

  • Shrinks

  • Blebbing

  • Nucleus breaks down, breaks into small membrane wrapped fragments

  • Phagocyte signals

  • Apoptosis Video


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Importance of Apoptosis

  • Maturing organisms

  • Virus

  • Immune System

  • DNA damage


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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


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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


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Two Caspase Pathways

Extrinsic Pathway

Death Ligand

Death Receptors

Caspases

Cell Death


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Two Caspase Pathways

Intrinsic Pathway

Mitochondria

Cytochrome C

Apoptosome Complex

Caspases

Cell Death



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Cancer and Apoptosis

  • http://www.youtube.com/watch?v=qjjHKDn12qI

  • Evasion of apoptosis can lead to cancer


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Treatment Options

  • Activate apoptosis in cancer cells, problem solved.

  • Finding useful mechanisms

  • Needs to be selective

  • Pathways (trail)

  • IAPs

  • Seaweed?


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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


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Gene Expression

  • Down regulation of XIAP

    Most potent endogenous IAP

  • Using Adenovirus vector

  • ShRNA achieves delivery

    And long term inhibition