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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Cathepsin B contributes to bile salt-induced apoptosis of rat hepatocytes.

BACKGROUND & AIMS: Bile salt-induced apoptosis is mediated by a trypsin-like nuclear protease. The aims of this study were to identify this protease and to elucidate its mechanistic role in bile salt-induced hepatocyte apoptosis. METHODS: Rats, isolated rat hepatocytes, and a rat hepatoma cell line stably transfected with a bile salt transporter (McNtcp.24) were used for this study. RESULTS: In the bile duct-ligated rat, a threefold increase in apoptosis and a fourfold increase in trypsin-like nuclear protease activity were observed. The nuclear protease activity was purified from bile duct-ligated rats and identified as cathepsin B. Specific, structurally dissimilar cathepsin B inhibitors blocked glycochenodeoxycholate (GCDC)-induced apoptosis in cultured rat hepatocytes. Furthermore, stable transfection of McNtcp.24 cells with the complementary DNA for cathepsin B in the antisense orientation reduced cathepsin B activity and GCDC-induced apoptosis by >75%. Next, cathepsin B cellular localization during apoptosis was determined by immunoblot analysis of nuclear cell fractions, immunocytochemistry, and by determining the compartmentation of expressed cathepsin B fused to green fluorescent protein. All three approaches showed translocation of cathepsin B from the cytoplasm to the nucleus during GCDC-induced apoptosis. CONCLUSIONS: The data suggest that translocation of cathepsin B from the cytoplasm to the nucleus is a mechanism contributing to bile salt-induced apoptosis of hepatocytes.[1]

References

  1. Cathepsin B contributes to bile salt-induced apoptosis of rat hepatocytes. Roberts, L.R., Kurosawa, H., Bronk, S.F., Fesmier, P.J., Agellon, L.B., Leung, W.Y., Mao, F., Gores, G.J. Gastroenterology (1997) [Pubmed]
 
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