Superoxide as a signal for increase in intracellular pH.

We examined the role of superoxide in the increase in intracellular pH (pHi) of human histiocytic leukemia U937 cells treated with 4 beta-phorbol-12,13-didecanoate (4 beta-PDD) or serum. 4 beta-PDD or serum induced a rapid increase in pHi, and antioxidants such as superoxide dismutase (SOD), vitamin E, and butylated hydroxyanisole (BHA) were found to inhibit the amiloride-sensitive increase in pHi induced by 4 beta-PDD. SOD inhibited the increase in pHi caused by serum, and essentially the same was found in concanavalin A-stimulated mouse thymocytes. Also, a superoxide-generating system, xanthine-xanthine oxidase (X-XOD), increased pHi of U937 cells as much as 4 beta-PDD or serum. From these findings, it appears that superoxide is the basis for the modulation of pHi.