Cathepsin B increases apoptosis in fulminant hepatic failure

Mar 22 2009

The traditional view is that hepatocyte necrosis is the main feature of fulminant hepatic failure, but increasing evidence implicates a dominant role for hepatocyte apoptosis in this pathogenesis.

It is not known if cathepsin B-mediated hepatocyte apoptosis is involved in the pathogenesis of fulminant hepatic failure. To ascertain its pathogenic role in hepatic failure, the research examined the protective effect of a cathepsin B inhibitor (CA-074Me) on fulminant hepatic failure in mice.

A research article to be published on March 14, 2009 in the World Journal of Gastroenterology addresses this question. The research team led by Prof. Yang in the Department of Infectious Diseases of the Second Clinical Hospital of Harbin Medical University investigated cathepsin B expression changes in the liver of fulminant hepatic failure. The article further indicated that LPS/D-Gal N-mediated cathepsin B expression initiates hepatocyte apoptosis in fulminant hepatic failure.

Cathepsin B, a lysosomal cysteine protease, is a candidate for an apoptotic mediator originating from acidic vesicles. CA-074me is a selective inhibitor of cathepsin B , and it is highly cell-permeant and can decrease the expression or activity of cathepsin B. The traditional view is that hepatocyte necrosis is the main feature of fulminant hepatic failure, but increasing evidence implicates a dominant role for hepatocyte apoptosis in this pathogenesis. Inhibition of cathepsin B attenuates apoptosis and liver injury, supporting a link between cathepsin B and fulminant hepatic failure, and thus may provide new targets for further understanding of the pathogenesis of fulminant hepatic failure and new therapeutic targets.