Maeda S, Lin K H, Inagaki H, Saito T
Department of Chemistry, National Industrial Research Institute of Nagoya, Japan.
Biochem Mol Biol Int. 1996 Jun;39(3):447-53. doi: 10.1080/15216549600201491.
There is growing evidence that suggests the involvement of intracellular proteases in the process of apoptosis or programmed cell death. In this study, we have demonstrated that leupeptin, a cysteine protease inhibitor, can significantly increase the incidence of both apoptotic nuclear morphology change and internucleosomal DNA fragmentation in primary cultured hepatocytes in the absence of known apoptotic stimuli for hepatocytes. On the other hand, aspartic and serine protease inhibitors showed little or no effects on the apoptotic changes. In addition, we found that the apoptotic changes could be induced by chloroquine, an inhibitor of lysosomal proteolysis, but could not be induced by calpain inhibitors. These data suggest that inhibition of lysosomal cysteine proteases may induce apoptosis in primary cultured hepatocytes.
越来越多的证据表明，细胞内蛋白酶参与细胞凋亡或程序性细胞死亡过程。在本研究中，我们已经证明，在没有已知的肝细胞凋亡刺激因素的情况下，半胱氨酸蛋白酶抑制剂亮抑蛋白酶肽可显著增加原代培养肝细胞凋亡核形态改变和核小体间DNA片段化的发生率。另一方面，天冬氨酸和丝氨酸蛋白酶抑制剂对凋亡变化几乎没有影响。此外，我们发现溶酶体蛋白水解抑制剂氯喹可诱导凋亡变化，但钙蛋白酶抑制剂不能诱导凋亡变化。这些数据表明，溶酶体半胱氨酸蛋白酶的抑制可能诱导原代培养肝细胞凋亡。
