NDLI: Cathepsins as effector proteases in hepatocyte apoptosis

Content Provider	Springer Nature Link
Author	Roberts, Lewis R. Adjei, Philip N. Gores, Gregory J.
Copyright Year	1999
Abstract	Cathepsins B and D appear to act as part of the effector protease cascade in hepatocyte apoptosis, both in bile salt-induced apoptosis and CPT-induced apoptosis of hepatocellular cancer cell lines. It is important to note that these proteases do not appear to participate in many models of apoptosis studied to date; in fact, cathepsin inhibitors have been used as negative controls to show that enzymes other than caspases are not involved in apoptosis. In particular, it has been shown that cathepsin B inhibitors do not prevent many models of apoptosis in lymphocytes (43). Further, our experiments have shown that not all models of hepatocyte apoptosis are mediated by cathepsins. For example, staurosporine-induced apoptosis is not inhibited by cathepsin B inhibitors in primary hepatocytes or in cell lines stably transfected with the cathepsin B antisense construct. Although the signaling pathways leading to activation of cathepsins B and D in hepatocyte apoptosis are not completely understood, we hypothesize that a caspase 8-like protein may be involved proximal to cathepsins D and B (Fig. 6). The precise mechanism by which cathepsin B is translocated from lysosomes to “apoptotic targets” is currently under investigation in our laboratory. Because of the relative promiscuity of cathepsin B as protease, it is likely that it is involved in nonspecific protein degradation in apoptotic bodies; however, cathepsin B has also been shown to degrade certain specific proteins, such as histones, which may be directly relevant to the apoptotic process. Further evaluation of the role of cathepsins B and D in apoptosis should include the determination of specific proteolytic targets that result in the biochemical and morphologic manifestations of apoptosis.
Starting Page	71
Ending Page	88
Page Count	18
File Format	PDF
ISSN	10859195
Journal	Cell Biochemistry and Biophysics
Volume Number	30
Issue Number	1
e-ISSN	15590283
Language	English
Publisher	Humana Press
Publisher Date	1999-01-01
Publisher Place	Totowa
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Biochemistry Pharmacology/Toxicology Biotechnology Cell Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Medicine Biochemistry Biophysics

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