Montaser Metwally, Lalmanach Gilles, Mach Lukas
Zentrum für Angewandte Genetik, Universität für Bodenkultur Wien, Austria.
Biol Chem. 2002 Jul-Aug;383(7-8):1305-8. doi: 10.1515/BC.2002.147.
Studies using inhibitors that reportedly discriminate between cathepsin B and related lysosomal cysteine proteinases have implicated the enzyme in a wide range of physiological and pathological processes. The most popular substance to selectively inhibit cathepsin B in vivo is CA-074Me, the methyl ester of the E-64 derivative CA-074. However, we now have found that CA-074Me inactivates both cathepsin B and cathepsin L within murine fibroblasts. In contrast, exposure of these cells to the parental compound CA-074 leads to the selective inhibition of endogenous cathepsin B, while intracellular cathepsin L remains unaffected. These results indicate that CA-074 rather than CA-074Me should be used to specifically inactivate cathepsin B within living cells.
据报道，使用对组织蛋白酶B和相关溶酶体半胱氨酸蛋白酶具有区分作用的抑制剂进行的研究表明，该酶参与了广泛的生理和病理过程。在体内选择性抑制组织蛋白酶B最常用的物质是CA-074Me，它是E-64衍生物CA-074的甲酯。然而，我们现在发现CA-074Me可使小鼠成纤维细胞内的组织蛋白酶B和组织蛋白酶L失活。相比之下，将这些细胞暴露于母体化合物CA-074会导致内源性组织蛋白酶B被选择性抑制，而细胞内的组织蛋白酶L不受影响。这些结果表明，应该使用CA-074而非CA-074Me来特异性地使活细胞内的组织蛋白酶B失活。
