Participation of cathepsins B and 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 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.
Shibata
M
M
Department of Cell Biology and Anatomy I, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Kanamori
S
S
Isahara
K
K
Ohsawa
Y
Y
Konishi
A
A
Kametaka
S
S
Watanabe
T
T
Ebisu
S
S
Ishido
K
K
Kominami
E
E
Uchiyama
Y
Y
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002401:Cathepsin B / Q000502:physiology*; D002402:Cathepsin D / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D008247:Lysosomes / Q000201:enzymology; D009414:Nerve Growth Factors / Q000494:pharmacology; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*; D051381:Rats
D016895:Culture Media, Serum-Free; D009414:Nerve Growth Factors; D002401:Cathepsin B; D002402:Cathepsin D