Pyrogallol-induced As4.1 juxtaglomerular cell death is attenuated by MAPK inhibitors via preventing GSH depletion.

Pyrogallol (PG) induces apoptosis in several types of cells mediated by superoxide anion (O(2*-)). Here, we investigated the effects of PG and/or MAPK (MEK, JNK, and p38) inhibitors on the changes in cell growth, cell death, reactive oxygen species (ROS), and GSH levels in As4.1 juxtaglomerular (JG) cells. PG inhibited the growth of As4.1 cells. It also induced apoptosis and the loss of mitochondrial membrane potential (MMP; DeltaPsi(m)) and increased the level of p53 protein. Intracellular O2(*-) level was increased in PG-treated As4.1 cells. PG also increased the number of GSH deleted cells in As4.1 cells. All the MAPK inhibitors significantly attenuated the growth inhibition and death mediated by PG. They decreased the levels of p53 protein and MMP (DeltaPsi(m)) loss in PG-treated As4.1 cells. They also reduced O2(*-) level and GSH-depleted cell number in these cells. In conclusion, MAPK inhibitors attenuated As4.1 cell growth inhibition and death mediated by PG treatment. The changes in O2(*-) and GSH levels by PG and/or MAPK inhibitors appeared to affect the growth and death of As4.1 cells.