The Cathepsin B-Selective Inhibitors CA-074 and CA-074Me Inactivate Cathepsin L Under Reducing Conditions

Steverding, D (2011) The Cathepsin B-Selective Inhibitors CA-074 and CA-074Me Inactivate Cathepsin L Under Reducing Conditions. The Open Enzyme Inhibition Journal, 4 (1). pp. 11-16. ISSN 1874-9402

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Abstract

The inhibitor CA-074 and its membrane-permeable derivative CA-074Me have been widely employed to study the biological function of cathepsin B. These compounds have been described as selective inactivators of cathepsin B with barely detectable action on other cathepsins. However, in this study it is demonstrated that CA-074 and CA-074Me also inactivate cathepsin L in the presence of the thiol reagents dithiothreitol and glutathione. In addition, it is also found that CA-074Me inactivates cathepsin B in the presence of dithiothreitol, an inhibition reaction previously not described. Furthermore, it is shown that CA-074 and CA-074Me are able to inhibit cathepsin L within living HL-60 cells and bloodstream forms of Trypanosoma brucei brucei. For HL-60 cells it is also shown that the inhibition of cathepsin L by the inhibitors is due to the reducing intracellular environment. These results suggest that CA-074 and CA-074Me are not suitable to discriminate between cathepsin B and L in vivo. Accordingly, previous demonstrations of the involvement of cathepsin B in physiological and pathological processes probably need re-evaluation.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Related URLs:
Depositing User: Rhiannon Harvey
Date Deposited: 12 Dec 2011 15:07
Last Modified: 21 Apr 2020 16:53
URI: https://ueaeprints.uea.ac.uk/id/eprint/35697
DOI: 10.2174/1874940201104010011

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