Rapid suppression of free radical formation by nerve growth factor involves the mitogen-activated protein kinase pathway

Laura L. Dugan, Douglas J. Creedon, Eugene M. Johnson, David M. Holtzman

Research output: Contribution to journalArticle

115 Scopus citations

Abstract

Neurotrophins such as nerve growth factor (NGF) regulate neuronal survival during development and are neuroprotective in certain models of injury to both the peripheral and the central nervous system. Although many effects of neurotrophins involve long-term changes in gene expression, several recent reports have focused on rapid effects of neurotrophins that do not involve synthesis of new gene products. Because enhanced formation of reactive oxygen species (ROS) represents one consequence of many insults that produce neuronal death, we hypothesized that neurotrophins might influence neuronal function and survival through acute alterations in the production of ROS. Using an oxidation-sensitive compound, dihydrorhodamine, we measured ROS formation in a central nervous system-derived neuronal cell line (GT1-1 trk) and in superior cervical ganglion neurons, both of which express the transmembrane NGF receptor tyrosine kinase, trkA. There was enhanced production of ROS generation in GT1-1 trk cells occurred within 10 min. NGF suppression of ROS formation was prevented by PD 098059, a specific inhibitor of MEK (mitogen/extracellular receptor kinase, which phosphorylates mitogen- activated protein kinase). The observation that NGF acutely blocks ROS formation in neurons through activation of the mitogen-activated protein kinase pathway suggests a novel mechanism for understanding neuroprotective and other effects of neurotrophins.

Original languageEnglish
Pages (from-to)4086-4091
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume94
Issue number8
DOIs
StatePublished - Apr 15 1997

Keywords

  • cell culture
  • confocal microscopy
  • mitochondria
  • neurotrophin
  • reactive oxygen species

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