intrinsic apoptosis pathway intrinsic apoptosis pathway marieta garib aisha green linda miranda
TRANSCRIPT
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INTRINSIC APOPTOSIS PATHWAY
Marieta GaribAisha Green
Linda Miranda
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WHAT IS INTRINSIC APOPTOSIS AND WHY DO WE CARE?
•Programmed cell-death involving permeability of mitchondria.Involves Caspase-9•As opposed to extrinsic.Tumor necrosis factorCaspase-8No mitochondria
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WHAT IS INTRINSIC APOPTOSIS AND WHY DO WE CARE?
•Intrinsic pathway induced by chemotherapeutic agents.
•Activation or downregulation of apoptosis influence cancer cell viability.
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http://www.qiagen.com/GeneGlobe/Pathways/Mitochondrial%20Apoptosis.jpg
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•Caspase 3 Activation = 377.940 seconds•1 Molecule = 477.740 seconds
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•Activation = 394.350 seconds•.99 Caspase-3 = 477.740 seconds
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•Activation = 306.390 seconds•.98 molecule Caspase-3 = 484.900
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•Caspase-3 is activated at 250.250 sec.•1 molecule 499.490 sec.
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200.000 250.000 300.000 350.000 400.000 450.000 500.000 550.0000
0.2
0.4
0.6
0.8
1
1.2
Rate of Activation of Caspase 3
10,000 nM dATP
Time (seconds)
Casp
ase
3 M
olec
ules
•Activation = 239.044 secs•1 molecule = 490.759 secs
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•Activation = 229.350 secs•1 molecule = 497.330 secs
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150.000 200.000 250.000 300.000 350.000 400.000 450.000 500.0000.000
0.200
0.400
0.600
0.800
1.000
1.200
Rate of Activation of Caspase 3
20,000 nM dATP
Time (seconds)
Casp
ase
3 M
olec
ules
•Active holoenzyme at 177.137 seconds.•1 molecule of Caspase-3 at 415.351 seconds
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Problems and Issues
•choice between intrinsic and extrinsic pathways •finding a target molecule to test
•complexity of the chemical reactions and large number of molecules observed
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Problems and Issues
•difficulty with ODE simulation •long running time of the program due to the complexity of the reactions and the large number of molecules examined
•long t_end=>500 to produce results •very long .gdat files
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CONCLUSIONS
•Varying the concentrations of ATP affects the formation of the holoenzyme
Higher = faster activation of Caspase-3Lower = longer activation time
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FUTURE EXPERIMENTS
•Vary concentrations of Apaf-1 and Cytochrome C
•Will they affect holoenzyme formation?