Yamaguchi Takeo, Hashiguchi Kenji, Katsuki Satoshi, Iwamoto Wakako, Tsuruhara Shoichiro, Terada Shigeyuki
Department of Chemistry, Faculty of Science, Fukuoka University, Jonan-ku, Fukuoka, 814-0180, Japan.
Cell Mol Biol Lett. 2008;13(1):49-57. doi: 10.2478/s11658-007-0034-x. Epub 2007 Oct 19.
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.
我们之前证明，凋亡执行者半胱天冬酶-3在压力诱导的小鼠红白血病（MEL）细胞凋亡（100兆帕）中被激活。在此，我们使用肽底物和半胱天冬酶抑制剂研究了半胱天冬酶-3的激活途径。使用半胱天冬酶-8和-9的底物，发现二者在高压下的细胞中均被激活。半胱天冬酶-8和-9以及泛半胱天冬酶抑制剂可抑制100兆帕处理的MEL细胞中具有亚G1期DNA含量的细胞核的产生。在100兆帕处理的细胞中，泛半胱天冬酶抑制剂部分阻止了细胞色素c从线粒体的释放以及线粒体膜电位的破坏。这些结果表明，在MEL细胞高压诱导死亡过程中的凋亡信号传导中，内源性和外源性途径均被激活。
