Increased production of reactive oxygen species by the vacuolar-type (H+)-ATPase inhibitors bafilomycin A1 and concanamycin A in RAW 264 cells

Treatment of the mouse leukemic cell line RAW 264 with bafilomycin A1 or concanamycin A, inhibitors of vacuolar-type (H+)-ATPases (V-ATPases), significantly increased the production of reactive oxygen species (ROS) and decreased cell viability. These effects were significantly suppressed by the presence of N-acetyl cysteine (NAC), an ROS scavenger. si-RNA mediated knockdown of the gene for the c subunit of the V0 domain of V-ATPase also resulted in an increase in ROS production and a decrease in cell viability. These results suggest that decreased cellular V-ATPase activity decreases cell viability by increasing ROS production in RAW 264 cells.