A Comprehensive Systems Biological Study of Autophagy-Apoptosis Crosstalk during Endoplasmic Reticulum Stress

Figure 5

The role of autophagy to determine the activation threshold for apoptosis. HepG2 cells were pretreated with autophagy inhibitor ((a) and (b) 1 mM 3-methyladenine for 2 hours) or activator ((c) 100 μM metyrapone for 2 hours) before low ((a) 1 μM) or high ((b) and (c) 100 μM) level of 4-hour long TM treatment and the main autophagy (p62) and apoptosis markers (cleaved PARP) were followed in time by immunoblotting ((a), (b), and (c)). The percentage of apoptotic cells was followed by Annexin dye (errors bars represent standard deviation; asterisks indicate statistically significant difference from the control: ; ) ((d), (e), and (f)). ((d)-(e)-(f)) The mathematical simulation of single cell treatment. ((d) and (e)) The activation term of autophagy inducer reduced to kaau’ = 0.2, while S0 = 1 on (d) and 5 on (e). (f) The activation term of autophagy inducer increased to kaau’ = 0.7 and S0 = 5.

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