apoptosis “cell death” by brian abadie, emily anderson, andjohn ramsey
TRANSCRIPT
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 DNA
damage
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
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
Extrinsic Pathway
Death Ligand
Death Receptors
Caspases
Cell Death
Intrinsic Pathway
Mitochondria
Cytochrome C
Apoptosome
Complex
Caspases
Cell Death
Two Caspase Pathways
Two Caspase Pathways
Cancer and Apoptosis
http://www.youtube.com/watch?v=qjjHKDn12qI
Evasion of apoptosis can lead to cancer
Treatment Options
Activate apoptosis in cancer cells, problem solved.
Finding useful mechanisms Needs to be selective Pathways (trail) IAPs Seaweed?
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
Gene Expression
Down regulation of XIAPMost potent endogenous IAP Using Adenovirus vector ShRNA achieves deliveryAnd long term inhibition