PARTICIPATION OF CATHEPSIN-B AND CATHEPSIN-D IN APOPTOSIS OF PC12 CELLS FOLLOWING SERUM DEPRIVATION

Cathepsin D, a lysosomal aspartic proteinase, has been shown to induce apoptosis of HeLa cells when overexpressed. To further understand reg ulatory mechanisms of cathepsin D-induced cell death, we examined whet her lysosomal cysteine and aspartic proteinases are involved in apopto sis of PC12 cells following serum deprivation. In serum deprived cultu re, 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 catheps in B was drastically reduced 24 hr after the onset of culture, whereas that of cathepsin D considerably increased. The viability of PC12 cel ls overexpressing cathepsin B was significantly higher in serum-depriv ed culture than wild-type cells. In this situation, the amount of the cathepsin B protein did not decrease. The results suggest that there e xists an apoptotic pathway regulated by lysosomal cathepsins B and D. (C) 1998 Academic Press.