![Page 1: APOPTOSIS “Cell Death” By Brian Abadie, Emily Anderson, andJohn Ramsey](https://reader036.vdocuments.net/reader036/viewer/2022062421/56649d925503460f94a79231/html5/thumbnails/1.jpg)
APOPTOSIS“Cell Death”By Brian Abadie, Emily Anderson, andJohn Ramsey
![Page 2: APOPTOSIS “Cell Death” By Brian Abadie, Emily Anderson, andJohn Ramsey](https://reader036.vdocuments.net/reader036/viewer/2022062421/56649d925503460f94a79231/html5/thumbnails/2.jpg)
Characteristics of Apoptosis
Shrinks Blebbing Nucleus breaks
down, breaks into small membrane wrapped fragments
Phagocyte signals
Apoptosis Video
![Page 3: APOPTOSIS “Cell Death” By Brian Abadie, Emily Anderson, andJohn Ramsey](https://reader036.vdocuments.net/reader036/viewer/2022062421/56649d925503460f94a79231/html5/thumbnails/3.jpg)
Importance of Apoptosis
Maturing organisms
Virus Immune
System DNA
damage
![Page 4: APOPTOSIS “Cell Death” By Brian Abadie, Emily Anderson, andJohn Ramsey](https://reader036.vdocuments.net/reader036/viewer/2022062421/56649d925503460f94a79231/html5/thumbnails/4.jpg)
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
![Page 5: APOPTOSIS “Cell Death” By Brian Abadie, Emily Anderson, andJohn Ramsey](https://reader036.vdocuments.net/reader036/viewer/2022062421/56649d925503460f94a79231/html5/thumbnails/5.jpg)
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
![Page 6: APOPTOSIS “Cell Death” By Brian Abadie, Emily Anderson, andJohn Ramsey](https://reader036.vdocuments.net/reader036/viewer/2022062421/56649d925503460f94a79231/html5/thumbnails/6.jpg)
Two Caspase Pathways
Extrinsic Pathway
Death Ligand
Death Receptors
Caspases
Cell Death
![Page 7: APOPTOSIS “Cell Death” By Brian Abadie, Emily Anderson, andJohn Ramsey](https://reader036.vdocuments.net/reader036/viewer/2022062421/56649d925503460f94a79231/html5/thumbnails/7.jpg)
Intrinsic Pathway
Mitochondria
Cytochrome C
Apoptosome
Complex
Caspases
Cell Death
Two Caspase Pathways
![Page 8: APOPTOSIS “Cell Death” By Brian Abadie, Emily Anderson, andJohn Ramsey](https://reader036.vdocuments.net/reader036/viewer/2022062421/56649d925503460f94a79231/html5/thumbnails/8.jpg)
Two Caspase Pathways
![Page 9: APOPTOSIS “Cell Death” By Brian Abadie, Emily Anderson, andJohn Ramsey](https://reader036.vdocuments.net/reader036/viewer/2022062421/56649d925503460f94a79231/html5/thumbnails/9.jpg)
Cancer and Apoptosis
http://www.youtube.com/watch?v=qjjHKDn12qI
Evasion of apoptosis can lead to cancer
![Page 10: APOPTOSIS “Cell Death” By Brian Abadie, Emily Anderson, andJohn Ramsey](https://reader036.vdocuments.net/reader036/viewer/2022062421/56649d925503460f94a79231/html5/thumbnails/10.jpg)
Treatment Options
Activate apoptosis in cancer cells, problem solved.
Finding useful mechanisms Needs to be selective Pathways (trail) IAPs Seaweed?
![Page 11: APOPTOSIS “Cell Death” By Brian Abadie, Emily Anderson, andJohn Ramsey](https://reader036.vdocuments.net/reader036/viewer/2022062421/56649d925503460f94a79231/html5/thumbnails/11.jpg)
IAPs
Inhibitor of Apoptosis ProteinsNeutralize them or prevent their
production Inhibit one part in the cascade =
failure to apoptose Smac mimetics Bcl proteins Elevated BclConfers resistance to chemotherapy
![Page 12: APOPTOSIS “Cell Death” By Brian Abadie, Emily Anderson, andJohn Ramsey](https://reader036.vdocuments.net/reader036/viewer/2022062421/56649d925503460f94a79231/html5/thumbnails/12.jpg)
Gene Expression
Down regulation of XIAPMost potent endogenous IAP Using Adenovirus vector ShRNA achieves deliveryAnd long term inhibition