title: Activation of the intrinsic and extrinsic pathways in high pressure-induced apoptosis of murine erythroleukemia cells.
abstract: 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.
authors.affiliation: Department of Chemistry, Faculty of Science, Fukuoka University, Jonan-ku, Fukuoka, 814-0180, Japan. takeo@fukuoka-u.ac.jp
authors.forename: Takeo
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Hashiguchi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Katsuki
authors.forename: Wakako
authors.initials: W
authors.lastname: Iwamoto
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Tsuruhara
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Terada
mesh_terms: 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*
chemical_list: D061945:Caspase Inhibitors; D020169:Caspases