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APOPTOSIS PowerPoint Presentation

APOPTOSIS

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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