Journal article

Demonstration of elevated levels of active cathepsin S in dextran sulfate sodium colitis using a new activatable probe

N Barlow, Y Nasser, P Zhao, N Sharma, R Guerrero-Alba, LE Edgington-Mitchell, T Lieu, NA Veldhuis, DP Poole, JW Conner, E Lindstrom, AW Craig, B Graham, SJ Vanner, NW Bunnett



BACKGROUND: Proteases play a major role in inflammatory diseases of the gastrointestinal tract. Activatable probes are a major technological advance, enabling sensitive detection of active proteases in tissue samples. Our aim was to synthesize an activatable probe for cathepsin S and validate its use in a mouse model of colitis. METHODS: We designed and synthesized a new fluorescent activatable probe, NB200, for the detection of active cathepsin S. Colitis was induced in C57BL/6 mice by the administration of 3% dextran sulfate sodium (DSS). Homogenized mouse colons, with or without the addition of the specific cathepsin S inhibitor MV026031, were incubated with NB200 in a fluorescent plate r..

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Funding Acknowledgements

This work was supported by a grant from the National Health and Medical Research Council Australia (NHMRC to NWB), Canadian Institutes of Health Research and Crohn's and Colitis Canada (CIHR and CCC to SV), and a joint fellowship from the CIHR/Canadian Association of Gastroenterology/CCC (to YN).