Enhancement of propyl gallate-induced calf pulmonary arterial endothelial cell death by MEK and JNK inhibitors

Propyl gallate (PG), a synthetic antioxidant, exerts a variety of effects on tissue and cell functions. Here, we investigated the effect of mitogen-activated protein kinase (MAPK) inhibitors on PG-treated calf pulmonary artery endothelial cells (CPAECs) in relation to changes in cell death, reactive oxygen species (ROS) and glutathione (GSH). PG inhibited CPAEC growth at 24 h and induced cell death, which was accompanied by the loss of mitochondrial membrane potential. PG also increased ROS levels in the CPAECs, while GSH depleted cell number. Treatment with MAPK (MEK, JNK and p38) inhibitors resulted in the slight enhancement of cell growth inhibition by PG. MEK and JNK inhibitors increased cell death and GSH depletion in PG-treated CPAECs without affecting ROS levels. In conclusion, PG inhibited the growth of CPAECs by regulating GSH levels. The pro-apoptotic effect of MEK and JNK inhibitors on PG-induced CPAEC death was related to a decrease in GSH levels.