PARTICIPATION OF REACTIVE OXYGEN SPECIES IN THE LYSOPHOSPHATIDIC ACID-STIMULATED MITOGEN-ACTIVATED PROTEIN-KINASE KINASE ACTIVATION PATHWAY

Recent evidence suggests that reactive oxygen species (ROS) may functi on as second messengers in intracellular signal transduction pathways. We explored the possibility that ROS were involved in lysophosphatidi c acid (LPA)-induced mitogen-activated protein (MAP) kinase signaling pathway in HeLa cells. Antioxidant N-acetylcysteine inhibited the LPA stimulated MAP kinase kinase activity. Direct exposure of HeLa cells t o hydrogen peroxide resulted in a concentration- and time-dependent ac tivation of MAP kinase kinase. Inhibition of catalase with aminotriazo le enhanced the effect of LPA on induction of MAP kinase kinase. Furth er, LPA stimulated ROS production in HeLa cells. These findings sugges t that ROS participate in the LPA-elicited MAP kinase signaling pathwa y.