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.
Yamaguchi
Takeo
T
Department of Chemistry, Faculty of Science, Fukuoka University, Jonan-ku, Fukuoka, 814-0180, Japan. takeo@fukuoka-u.ac.jp
Hashiguchi
Kenji
K
Katsuki
Satoshi
S
Iwamoto
Wakako
W
Tsuruhara
Shoichiro
S
Terada
Shigeyuki
S
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000502:physiology; D045744:Cell Line, Tumor; D002469:Cell Separation; D005434:Flow Cytometry; D004915:Leukemia, Erythroblastic, Acute / Q000201:enzymology / Q000473:pathology*; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D051336:Mitochondrial Membranes / Q000201:enzymology / Q000473:pathology; D011312:Pressure; D015398:Signal Transduction / Q000502:physiology*
D061945:Caspase Inhibitors; D020169:Caspases