Hydrostatic pressure induces apoptosis in the human leukaemic T-cell line Jurkat via the mitochondrial pathway.
We investigated the effect of pressure levels ranging from 80 to 500 bar on the proliferative capacity and viability of Jurkat leukaemic T cells. Pressurization at 360 bar induced apoptotic cell death as shown by apoptotic morphology after Hoechst staining, DNA fragmentation in the TdT-mediated dUTP nick end labelling-assay and cleavage of several caspase substrates. Cell death could be prevented by the general caspase inhibitor zVAD-fmk. Breakdown of the mitochondrial membrane potential and the release of cytochrome c provided strong evidence for an involvement of the mitochondrial pathway, whereas a central role of the death receptor pathway was excluded because caspase-8 was not significantly activated. Pressure incubation led to calcium influx after 5 min, and we hypothesize that calcium influx could be the primary trigger for pressure-induced apoptosis.
Klett
M V
MV
Biotechnology Institute Thurgau, Taegerwilen, Switzerland.
Boneberg
E-M
EM
Trenz
K
K
Knippers
R
R
Illges
H
H
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D020013:Calcium Signaling; D053181:Caspase 8; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004249:DNA Damage; D006801:Humans; D006874:Hydrostatic Pressure / Q000009:adverse effects*; D019169:Jurkat Cells; D015458:Leukemia, T-Cell / Q000378:metabolism / Q000473:pathology; D008928:Mitochondria / Q000378:metabolism*
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases