Transcriptomic analysis unveils correlations between regulative apoptotic caspases and genes of cholesterol homeostasis in human brain
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: raffaella picco
PROVIDER: E-GEOD-61388 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:This the model used in the article:
Quantitative analysis of pathways controlling extrinsic apoptosis in single cells.
Albeck JG, Burke JM, Aldridge BB, Zhang M, Lauffenburger DA, Sorger PK. Mol Cell.
2008 Apr 11;30(1):11-25.
PMID: 18406323
, doi: 10.1016/j.molcel.2008.02.012
Abstract:
Apoptosis in response to TRAIL or TNF requires the activation of initiator
caspases, which then activate the effector caspases that dismantle
cells and cause death. However, little is known about the dynamics
and regulatory logic linking initiators and effectors. Using a combination
of live-cell reporters, flow cytometry, and immunoblotting, we find
that initiator caspases are active during the long and variable delay
that precedes mitochondrial outer membrane permeabilization (MOMP)
and effector caspase activation. When combined with a mathematical
model of core apoptosis pathways, experimental perturbation of regulatory
links between initiator and effector caspases reveals that XIAP and
proteasome-dependent degradation of effector caspases are important
in restraining activity during the pre-MOMP delay. We identify conditions
in which restraint is impaired, creating a physiologically indeterminate
state of partial cell death with the potential to generate genomic
instability. Together, these findings provide a quantitative picture
of caspase regulatory networks and their failure modes.
The mitochondrial compartment is just added as a logical partition and its volume is not used in the mathematical formulas, to stick closer to the expressions used in the matlab files distributed with the original publication. There only the rate constants for bimolecular reactions are adapted by division by v
, the ration of the volumes of the mitochondrial compartment and the total cell.
For BCL2 overexpression in figure 5, the initial BCL2 amount was increased by a factor 12 to 2.4*10 5
. For siRNA downregulation of XIAP its amount was multiplied by 0.13 to 1.3*10 4
.
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2009-07-01 | BIOMD0000000220 | BioModels