Interestingly, the pan-caspase inhibitor z-Val-Ala-DL-Asp-fluoromethylketone (z-VAD-FMK) and the JAK2 tyrosine kinase inhibitor AG490 both inhibited cleavage dose-dependently, and cleavage was significantly lower in a heterozygous JAK2 knockout ES cell clone.
The zVAD-fmk or IETD-fmk inhibited RIP1 cleavage dose-dependently in striatal cells (Supplementary Figure S1c), thus facilitating RIP1 kinase activation and subsequent necroptosis, whereas Nec-1 rescued striatal cell death and restored the normal status of RIP1 cleavage in zVAD-fmk/IETD-fmk-treated cells to the similar level as untreated control cells.
P53-deficient cells showed PARP cleavage after a dose of 30 mM LiCl, while cleavage of Caspase-3 was already visible after a dose of 15 mM LiCl (Additional file 3, Figure S3A).
We have shown that Ag-NPs decrease the efficiency of cathepsin cleavage in a dose-dependent manner with significant effects observed at doses as low as 1 5 μg/ml, which is non-toxic to the cell itself.
These results indicated that NSAIDs induced PARP cleavage in a dose-dependent manner, thus suggesting an induction of apoptosis.
Compounds 3, 5, 7, 8 and 11 displayed their protective properties on DNA cleavage in a dose-dependent manner.
Glycine stimulates cleavage in a dose-dependent manner: the higher the concentration of glycine, the greater is the decrease in uncleaved and subsequent increase in cleaved gpASNase3.
In parallel, LPV treatment induced PARP-1 cleavage in a dose-dependent manner, as measured by the specific accumulation of an 89 kDa fragment in cells.
However, combined treatment with cafestol and ABT-737 resulted in induction of sub-G1 population and PARP cleavage in a dose-dependent manner.
The data showed that SW IV-52s and SW III-123, but not SW43, triggered pro-caspase-8, -9 and -3 cleavage in a dose-dependent manner after 24-h treatment.
Immunoblotting analysis of whole cell extracts showed that z-VAD-FMK could inhibit STAT3α cleavage in a dose-dependent manner, with the generation of the 43 kDa and 48 kDa carboxyl- and amino-terminal fragments essentially abolished in the presence of 60 μM z-VAD-FMK (Fig. 2B, lanes 1, 2, 6 8, C-terminal STAT3α and N-terminal STAT3 panels).
