A PROTEOLYTIC ACTIVITY ENHANCED BY ARSENITE IN CHINESE-HAMSTER OVARY CELLS - POSSIBLE INVOLVEMENT IN ARSENITE-INDUCED CELL-KILLING

Treatment of Chinese hamster ovary (CHO-K1) cells with 10 mu M sodium arsenite for 24 h resulted in enhancement of a proteolytic activity toward the chromogenic substrate CBZ-Phe-Arg-AMC. Presence of dithiothreitol and a pH between 4 and 6 were required for displaying its full hydrolytic activity. According to its substrate- and inhibitor-specificity, this arsenite-induced proteolytic activity was very similar to lysosomal cathepsin B. Arsenite cytotoxicity was further shown to be partially prevented by inhibitors that inhibited the arsenite-induced protease, such as antipain and chymostatin, but not by protease inhibitors without inhibitory effects on the arsenite-induced protease. Our present results suggest that the arsenite-induced protease activity may be involved in arsenite's killing effects. (C) 1994 Academic Press, Inc.