التفاصيل البيبلوغرافية
| العنوان: |
Demonstration of elevated levels of active cathepsin S in dextran sulfate sodium colitis using a new activatable probe. |
| المؤلفون: |
Barlow, N., Nasser, Y., Zhao, P., Sharma, N., Guerrero‐Alba, R., Edgington‐Mitchell, L. E., Lieu, T., Veldhuis, N. A., Poole, D. P., Conner, J. W., Lindström, E., Craig, A. W., Graham, B., Vanner, S. J., Bunnett, N. W. |
| المصدر: |
Neurogastroenterology & Motility; Nov2015, Vol. 27 Issue 11, p1675-1680, 6p |
| مصطلحات موضوعية: |
ELECTRONIC probes, DIAGNOSTIC equipment, CATHEPSINS, COLITIS, INFLAMMATION, PROTEOLYTIC enzymes |
| مستخلص: |
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 C57 BL/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 reader. Key Results NB200 selectively detected purified cathepsin S and not other common inflammatory proteases. Homogenates of colon from mice with DSS colitis induced a significant fluorescent increase when compared to control animals (control vs DSS: p < 0.05 at 200 min and p < 0.01 at 220-240 min), indicating cathepsin S activation. The cathepsin S inhibitor abolished this increase in fluorescence ( DSS vs DSS + MV026031: p < 0.05 at 140 min, p < 0.01 at 180 min, p < 0.001 at 200-240 min), which confirms cathepsin S activation. Cathepsin S activity correlated with the disease activity index (Spearman r = 0.77, p = 0.017). Conclusions & Inferences Our investigation has demonstrated the utility of activatable probes for detecting protease activity in intestinal inflammation. Panels of such probes may allow 'signature' protease profiles to be established for a range of inflammatory diseases and disorders. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
