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Activation of the intrinsic and extrinsic pathways in high pressure-induced apoptosis of murine erythroleukemia cells


We previously demonstrated that caspase-3, an executioner of apoptosis, is activated in the pressure-induced apoptosis of murine erythroleukemia (MEL) cells (at 100 MPa). Here, we examined the pathway of caspase-3 activation using peptide substrates and caspase inhibitors. Using the substrates of caspases-8 and -9, it was found that both are activated in cells under high pressure. The production of nuclei with sub-G1 DNA content in 100 MPa-treated MEL cells was suppressed by inhibitors of caspases-8 and -9, and pan-caspase. In 100 MPa-treated cells, pan-caspase inhibitor partially prevented the cytochrome c release from the mitochondria and the breakdown of mitochondrial membrane potential. These results suggest that the intrinsic and extrinsic pathways are activated in apoptotic signaling during the high pressure-induced death of MEL cells.









caspase-activated deoxyribo-nuclease




4-(2-hydroxyethyl)piperazine-1-ethanesulfonic acid


murine erythroleukemia


nonidet P-40


phosphate-buffered saline


propidium iodide


phenylmethanesulfonyl fluoride

RNase A:

ribonuclease A


reactive oxygen species




benzyloxycarbonyl-Ile-Glu(OMe)-Thr-Asp(OMe)-fluoromethyl ketone


benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethyl ketone


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Correspondence to Takeo Yamaguchi.

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Yamaguchi, T., Hashiguchi, K., Katsuki, S. et al. Activation of the intrinsic and extrinsic pathways in high pressure-induced apoptosis of murine erythroleukemia cells. Cell Mol Biol Lett 13, 49–57 (2008).

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Key words

  • Apoptosis
  • Caspases
  • Cytochrome c
  • Flow cytometry
  • Membrane potential
  • High pressure