Cell proliferation induced by reactive oxygen species is mediated via mitogen-activated protein kinase in Chinese hamster lung fibroblast (V79) cells.

Abstract Reactive oxygen species (ROS) are generated during cellular metabolism or by external factors. Recently, it was learned that ROS can stimulate cellular proliferation and act as a second messenger in cellular signaling. We previously reported that hydroxyl radicals might be the signaling molecules. In the present experiment, phenazine methosulfate (PMS) was used to generate superoxide anion intracellularly. Treatment with 3 microM PMS in V79 cells increased cellular proliferation by 50%. PMS also activated the c-Jun N-terminal kinase (JNK) and p38 MAPK, but not extracellular signal-regulated kinase (ERK) 1/2 and ERK5. In particular, increased proliferation was blocked by pretreatment with SB203580 (an inhibitor of p38 MAPK). At the transcriptional level, the phosphorylation of c-Jun and ATF-2, which are mediated by JNK and p38 MAPK, were also increased by treatment with PMS.