Decrease in cytosolic phospholipase A2alpha mRNA levels by reactive oxygen species via MAP kinase pathways in PC12 cells: effects of dopaminergic neurotoxins.
Excess production of reactive oxygen species (ROS), including H2O2, leads to neuronal death in pathological conditions. Although ROS stimulates alpha-type cytosolic phospholipase A2 (cPLA2alpha) activity, their role in cPLA2alpha expression has not been elucidated. We investigated the effect of ROS on cPLA2alpha mRNA levels and signaling pathways in rat pheochromocytoma PC12 cells. Treatment with H2O2 and xanthine-xanthine oxidase (X/XO) for 4 h decreased cPLA2alpha mRNA levels without changing the mRNA levels of other tested proteins. H2O2 and X/XO caused cell toxicity not after 4 h but 24 h after their addition. The H2O2-induced decrease in cPLA2alpha 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 cPLA2alpha mRNA levels. These findings suggest that ROS decreases cPLA2alpha mRNA levels via MAPK pathways in PC12 cells.
Akiyama
Nobuteru
N
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan.
Shimma
Naoko
N
Takashiro
Yuko
Y
Hatori
Yoshio
Y
Hirabayashi
Tetsuya
T
Horie
Syunji
S
Saito
Takashi
T
Murayama
Toshihiko
T
D015655:1-Methyl-4-phenylpyridinium / Q000494:pharmacology*; D000818:Animals; D015536:Down-Regulation; D005786:Gene Expression Regulation; D054513:Group IV Phospholipases A2; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D016716:PC12 Cells; D010741:Phospholipases A / Q000235:genetics / Q000378:metabolism*; D054467:Phospholipases A2; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*
D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D044005:Tetrahydroisoquinolines; C014843:1,2,3,4-tetrahydroisoquinoline; D006861:Hydrogen Peroxide; D010741:Phospholipases A; D054513:Group IV Phospholipases A2; D054467:Phospholipases A2; D015655:1-Methyl-4-phenylpyridinium