The effects of MAPK inhibitors on antimycin A-treated calf pulmonary arterial endothelial cells in relation to cell death, reactive oxygen species and glutathione

Antimycin A (AMA) inhibits succinate oxidase and the mitochondrial electron transport chain between cytochrome b and c. Here, we report on the effects of mitogen-activated protein kinase (MAPK) inhibitors on AMA-treated calf pulmonary artery endothelial cells (CPAEC) in relation to cell death, reactive oxygen species (ROS) and glutathione (GSH). AMA inhibited the growth of CPAEC and also induced cell death, which was accompanied by the loss of mitochondrial membrane potential (MMP; Δψ_m). AMA increased ROS levels including O₂^·-, and depleted GSH cell numbers in CPAEC. All the MAPK (MEK, JNK, p38) inhibitors enhanced cell growth inhibition and death by AMA, and appeared to augment ROS but not O₂^·- levels in AMA-treated CPAEC. MEK and p38 inhibitors did not increase the number of GSH-depleted cells in AMA-treated CPAEC, but JNK inhibitor significantly did. Each MAPK inhibitor affected cell growth, death, ROS and GSH levels differently in comparison to control CPAEC. In conclusion, the MAPK inhibitors enhanced cell growth inhibition and death by AMA. Changes in ROS and GSH levels by AMA and/or MAPK inhibitors affected growth and death in CPAEC.