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APOPTOSIS

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

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  1. APOPTOSIS “Cell Death” By Brian Abadie, Emily Anderson, andJohn Ramsey

  2. Characteristics of Apoptosis • Shrinks • Blebbing • Nucleus breaks down, breaks into small membrane wrapped fragments • Phagocyte signals • Apoptosis Video

  3. Importance of Apoptosis • Maturing organisms • Virus • Immune System • DNA damage

  4. 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

  5. 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

  6. Two Caspase Pathways Extrinsic Pathway  Death Ligand  Death Receptors  Caspases  Cell Death

  7. Two Caspase Pathways Intrinsic Pathway  Mitochondria  Cytochrome C  Apoptosome Complex  Caspases  Cell Death

  8. Two Caspase Pathways

  9. Cancer and Apoptosis • http://www.youtube.com/watch?v=qjjHKDn12qI • Evasion of apoptosis can lead to cancer

  10. Treatment Options • Activate apoptosis in cancer cells, problem solved. • Finding useful mechanisms • Needs to be selective • Pathways (trail) • IAPs • Seaweed?

  11. 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

  12. Gene Expression • Down regulation of XIAP Most potent endogenous IAP • Using Adenovirus vector • ShRNA achieves delivery And long term inhibition

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