Decrease in cytosolic phospholipase A 2α mRNA levels by reactive oxygen species via MAP kinase pathways in PC12 cells: effects of dopaminergic neurotoxins

Abstract

Excess production of reactive oxygen species (ROS), including H 2O 2, leads to neuronal death in pathological conditions. Although ROS stimulates α-type cytosolic phospholipase A 2 (cPLA 2α) activity, their role in cPLA 2α expression has not been elucidated. We investigated the effect of ROS on cPLA 2α mRNA levels and signaling pathways in rat pheochromocytoma PC12 cells. Treatment with H 2O 2 and xanthine–xanthine oxidase (X/XO) for 4 h decreased cPLA 2α mRNA levels without changing the mRNA levels of other tested proteins. H 2O 2 and X/XO caused cell toxicity not after 4 h but 24 h after their addition. The H 2O 2-induced decrease in cPLA 2α mRNA levels was inhibited in cells treated with N-acetyl-cysteine and selective inhibitors of mitogen-activated protein kinase (MAPK) pathways (extracellular signal-regulated kinase and p38 MAPK). Treatment with dopaminergic neurotoxins, including 1,2,3,4-tetrahydroisoquinoline (TIQ)-inducing ROS formation, decreased cPLA 2α mRNA levels. These findings suggest that ROS decreases cPLA 2α mRNA levels via MAPK pathways in PC12 cells.