4-Hydroxynonenal contributes to NGF withdrawal-induced neuronal apoptosis

Shane R. Bruckner, George Perry, Steven Estus

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Reactive oxygen species are a necessary triggering event for apoptosis of sympathetic neurons after nerve growth factor (NGF) withdrawal. Reactive oxygen species can lead to the generation of 4-hydroxynonenal (HNE), a highly reactive aldehyde that forms adducts with proteins. This covalent modification can activate or inhibit signal transduction pathways involved in the induction of apoptosis. This process may be clinically relevant because HNE-adduct immunoreactivity increases in several disease states. Here we evaluate the role of HNE-adducts in sympathetic neurons undergoing NGF-deprivation-induced apoptosis, a model of developmental programmed cell death. We show that HNE-adduct immunoreactivity is dramatically increased after NGF-withdrawal in an NADPH oxidase-dependent manner. Moreover, HNE-adducts appear to contribute to NGF-deprivation-induced apoptotic signal transduction because microinjected HNE-adduct antiserum protects sympathetic neurons from NGF withdrawal. In conclusion, this report suggests the direct contribution of endogenously generated HNE in the stimulation of apoptotic signal transduction in neurons.

Original languageEnglish
Pages (from-to)999-1005
Number of pages7
JournalJournal of Neurochemistry
Issue number4
StatePublished - May 2003


  • 4-hydroxynonenal
  • Apoptosis
  • NGF withdrawal
  • Oxidative stress
  • Sympathetic neuron

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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