Shibata M, Kanamori S, Isahara K, Ohsawa Y, Konishi A, Kametaka S, Watanabe T, Ebisu S, Ishido K, Kominami E, Uchiyama Y
Department of Cell Biology and Anatomy I, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Biochem Biophys Res Commun. 1998 Oct 9;251(1):199-203. doi: 10.1006/bbrc.1998.9422.
Cathepsin D, a lysosomal aspartic proteinase, has been shown to induce apoptosis of HeLa cells when overexpressed. To further understand regulatory mechanisms of cathepsin D-induced cell death, we examined whether lysosomal cysteine and aspartic proteinases are involved in apoptosis of PC12 cells following serum deprivation. In serum deprived culture, PC12 cells overexpressing cathepsin D died more rapidly than wild-type cells. When the active forms of cathepsins B and D were examined during the apoptotic process of wild-type cells, the amount of cathepsin B was drastically reduced 24 hr after the onset of culture, whereas that of cathepsin D considerably increased. The viability of PC12 cells overexpressing cathepsin B was significantly higher in serum-deprived culture than wild-type cells. In this situation, the amount of the cathepsin B protein did not decrease. The results suggest that there exists an apoptotic pathway regulated by lysosomal cathepsins B and D.
组织蛋白酶D是一种溶酶体天冬氨酸蛋白酶，研究表明，过表达时它可诱导HeLa细胞凋亡。为进一步了解组织蛋白酶D诱导细胞死亡的调控机制，我们检测了血清剥夺后溶酶体半胱氨酸和天冬氨酸蛋白酶是否参与PC12细胞的凋亡过程。在血清剥夺培养中，过表达组织蛋白酶D的PC12细胞比野生型细胞死亡更快。在野生型细胞凋亡过程中检测组织蛋白酶B和D的活性形式时，培养开始24小时后，组织蛋白酶B的量急剧减少，而组织蛋白酶D的量显著增加。在血清剥夺培养中，过表达组织蛋白酶B的PC12细胞的活力明显高于野生型细胞。在这种情况下，组织蛋白酶B蛋白的量没有减少。结果表明，存在一条由溶酶体组织蛋白酶B和D调控的凋亡途径。
