p38 inhibitor intensified cell death in antimycin A-treated As4.1 juxtaglomerular cells via the enhancement of GSH depletion

Antimycin A (AMA) inhibits succinate oxidase, NADH oxidase and mitochondrial electron transport chain between cytochrome b and c. Here, we investigated the effects of AMA and/or mitogen-activated protein kinase (MAPK) inhibitors on As4.I juxtaglomerular cells in relation to cell growth, cell death, reactive oxygen species (ROS) and glutathione (GSH) levels. Treatment with 50 nM AMA inhibited the growth of As4.1 cells at 48 hours and induced apoptosis, which was accompanied by the loss of mitochondrial membrane potential (Δψ_m). AMA increased ROS levels including that of intracellular 02̇̄. AMA also induced GSH depletion. MEK inhibitor did not affect cell growth, cell death, Δψ_m loss, ROS level or GSH depletion in AMA-treated As4.1 cells. c-Jun N-terminal kinase (JNK) inhibitor also did not influence cell growth, cell death, ROS level and GSH depletion but did slightly increase Δψ_m loss. Treatment with p38 inhibitor magnified cell growth inhibition by AMA and increased cell death, Δψ_m loss and GSH depletion in AMA-treated As4.1 cells. Conclusively, p38 inhibitor intensified cell death in AMA-treated As4.1 cells. The changes of GSH content rather than ROS level by AMA and/or MAPK inhibitors were more closely related to the growth and death of As4.1 cells.