The molecular effects of acrolein

J. P. Kehrer, S. S. Biswal

Research output: Contribution to journalReview article

Abstract

Acrolein is a highly electrophilic α,β-unsaturated aldehyde to which humans are exposed in a variety of environmental situations, particularly as a component of smoke. In addition, as a metabolite of cyclophosphamide, acrolein is a major factor in the toxicity and perhaps the therapeutic activity of this important anticancer agent. The exposures to acrolein that are attained in vivo in most situations are quite low and the effects may differ from those seen at acutely toxic doses. At low doses, acrolein inhibits cell proliferation without causing cell death and may enhance apoptosis from secondary toxins, while at higher doses oncosis ensues. Although the acute toxicology of acrolein has been extensively investigated, both in animals and cultured cells, little information exists on the molecular effects of this reactive aldehyde. It is possible that the acrolein-mediated decrease in cell proliferation is caused by effecting changes in the expression of one or more growth- or stress-related genes or transcription factors secondary to a reduction in glutathione (GSH), which is rapidly depleted following acrolein treatment. It is apparent that the activation of the transcription factors nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1) can be inhibited by acrolein. The purpose of this review is to assess the literature currently available on the molecular effects of acrolein, to discuss the relationship between effects on glutathione with those on various genes, and to present some new data showing that acrolein actively stimulates genes associated with the electrophile response element.

Original languageEnglish (US)
Pages (from-to)6-15
Number of pages10
JournalToxicological Sciences
Volume57
Issue number1
DOIs
StatePublished - Jan 1 2000
Externally publishedYes

Keywords

  • Acrolein
  • Activator protein 1 (AP-1)
  • Electrophile response element (ERE)
  • Gene array
  • Glutathione GSH)
  • Nuclear factor kappa-B (NF-κB)
  • Transcription factors

ASJC Scopus subject areas

  • Toxicology

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