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Temporal Heterogeneity In Apoptosis Execution
Author(s) -
Vorobjev Ivan,
Barteneva Natasha
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.978.4
Subject(s) - apoptosis , microbiology and biotechnology , staurosporine , jurkat cells , population , cell , biology , caspase , hela , programmed cell death , depolarization , mitochondrion , biophysics , immunology , t cell , genetics , signal transduction , immune system , demography , protein kinase c , sociology
Apoptotic process is highly heterogeneous, and a long‐standing question is what parameters define time and reversibility of the apoptotic response at a single cell level. Using multicolor fluorescence assay we characterized at a single‐cell and population levels sequence of apoptotic events induced by extrinsic (TRAIL) and intrinsic (staurosporine, actinomycin D and etoposide) apoptotic stimuli in Jurkat and HeLa cells. Regardless of the stimulus first visible event on a single cell level was rapid apoptotic volume decrease (AVD) and Na + influx tightly coordinated with mitochondria outer membrane permeabilization (MOMP) and mitochondrial depolarization. These events happened largely asynchronous in the cell population. Activation of caspases 3/7 is slow process at a single cell level. It always starts after MOMP with significant delay and caspase activity linearly accumulates in a given cell for several hours. Cell‐to‐cell variability of the beginning of MOMP is well approximated by Gaussian distribution with CV about 35‐40%, while the γ‐distribution model describes cell‐to‐cell variability in the pre‐MOMP and MOMP‐to‐caspase activation stages. Sorting different subpopulations after induction of apoptosis we show that cells with intact mitochondria can recover after washout of apoptotic stimulus, cells after MOMP recover rarely and cells with caspase 3/7 activity can not recover at all. We propose a double‐stroke model for apoptosis execution/cell recovery.