RRC ID 68566
Author Tsuji M, Inanami O, Kuwabara M.
Title Induction of neurite outgrowth in PC12 cells by alpha -phenyl-N-tert-butylnitron through activation of protein kinase C and the Ras-extracellular signal-regulated kinase pathway.
Journal J Biol Chem
Abstract The spin trap alpha-phenyl-N-tert-butylnitron (PBN) is widely used for studies of the biological effects of free radicals. We previously reported the protective effects of PBN against ischemia-reperfusion injury in gerbil hippocampus by its activation of extracellular signal-regulated kinase (ERK) and suppression of both stress-activated protein kinase and p38 mitogen-activated protein kinase. In the present study, we found that PBN induced neurite outgrowth accompanied by ERK activation in PC12 cells in a dose-dependent manner. The induction of neurite outgrowth was inhibited significantly not only by transient transfection of PC12 cells with dominant negative Ras, but also by treatment with mitogen-activated protein kinase/ERK kinase inhibitor PD98059. The activation of receptor tyrosine kinase TrkA was not involved in PBN-induced neurite outgrowth. A protein kinase C (PKC) inhibitor, GF109203X, was found to inhibit neurite outgrowth. The activation of PKCepsilon was observed after PBN stimulation. PBN-induced neurite outgrowth and ERK activation were counteracted by the thiol-based antioxidant N-acetylcysteine. From these results, it was concluded that PBN induced neurite outgrowth in PC12 cells through activation of the Ras-ERK pathway and PKC.
Volume 276(35)
Pages 32779-85
Published 2001-8-31
DOI 10.1074/jbc.M101403200
PII S0021-9258(20)77804-X
PMID 11438521
MeSH Acetylcysteine / pharmacology Androstadienes / pharmacology Animals Cyclic N-Oxides Egtazic Acid / analogs & derivatives Egtazic Acid / pharmacology Enzyme Activation Enzyme Inhibitors / pharmacology Flavonoids / pharmacology Free Radical Scavengers / pharmacology Indoles / pharmacology Isoquinolines / pharmacology Kinetics MAP Kinase Signaling System / drug effects MAP Kinase Signaling System / physiology* Maleimides / pharmacology Mitogen-Activated Protein Kinases / metabolism Neurites / drug effects Neurites / physiology* Neuroprotective Agents / pharmacology* Nitrogen Oxides / pharmacology* PC12 Cells Protein Kinase C / metabolism* Rats Recombinant Proteins / metabolism Signal Transduction / drug effects Signal Transduction / physiology* Sulfonamides* Transfection Wortmannin p38 Mitogen-Activated Protein Kinases ras Proteins / metabolism
IF 4.238
Human and Animal Cells PC-12(RCB0009)