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 journalArticle

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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