The lipid peroxidation product 4-hydroxy-2,3-nonenal inhibits constitutive and inducible activity of nuclear factor κB in neurons

Simonetta Camandola, Giuseppe Poli, Mark P. Mattson

Research output: Contribution to journalArticlepeer-review

Abstract

Peroxidation of membrane lipids occurs in many different neurodegenerative conditions including stroke, and Alzheimer's and Parkinson's diseases. Recent findings suggest that lipid peroxidation can promote neuronal death by a mechanism involving production of the toxic aldehyde 4-hydroxy-2,3-nonenal (HNE), which may act by covalently modifying proteins and impairing their function. The transcription factor NF-κB can prevent neuronal death in experimental models of neurodegenerative disorders by inducing the expression of anti-apoptotic proteins including Bcl-2 and manganese superoxide dismutase. We now report that HNE selectively suppresses basal and inducible NF-κB DNA binding activity in cultured rat cortical neurons. Immunoprecipitation-immunoblot analyses using antibodies against HNE-conjugated proteins and p50 and p65 NF-κB subunits indicate that HNE does not directly modify NF-κB proteins. Moreover, HNE did not affect NF-κB DNA-binding activity when added directly to cytosolic extracts, suggesting that HNE inhibits an upstream component of the NF-κB signaling pathway. Inhibition of the survival-promoting NF-κB signaling pathway by HNE may contribute to neuronal death under conditions in which membrane lipid peroxidation occurs.

Original languageEnglish (US)
Pages (from-to)53-60
Number of pages8
JournalMolecular Brain Research
Volume85
Issue number1-2
DOIs
StatePublished - Dec 28 2000

Keywords

  • Alzheimer's disease
  • AP-1
  • Apoptosis
  • Cerebral cortex
  • Nuclear factor κB
  • Stroke

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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