Comparative expression analysis reveals differences in the regulation of intestinal paraoxonase family members

Louis Philippe Precourt, Ernest Seidman, Edgard Delvin, Devendra Amre, Colette Deslandres, Michel Dominguez, Daniel Sinnett, Emile Levy

Research output: Contribution to journalArticlepeer-review

Abstract

The paraoxonase (PON) gene cluster contains three members (PON1, PON2, and PON3), located on chromosome 7q21.3-22.1. Until now there has been little insight into their regulation in human intestine. This study was designed to determine the regulation of PONs by oxidative stress and inflammatory factors. Differentiated Caco-2/15 cells, cultured on polycarbonate Transwell filter inserts, exhibited transcripts of the 3 PONs whereas Western blot revealed the protein expression of PON2 and PON3 only. Iron-ascorbate-mediated lipid peroxidation, lipopolysaccharides (LPS), tumor necrosis factor-α and interferon-γ induced differential effects on the gene expression and protein mass of PONs. In particular, LPS down-regulated PON2 protein expression, which was accompanied with decreased levels of IκBα, the inhibitor of the proinflammatory transcription factor nuclear factor-kappa B (NF-κB). Selective inactivation of NF-κB by the action of caffeic acid phenethyl ester (CAPE) partially attenuated but did not abolish LPS-triggered decline of PON2. However, the combination of CAPE and antioxidants completely abrogated the negative impact of LPS on PON2. Therefore, our data indicate that oxidative stress and proinflammatory agents selectively affect the expression of PONs. Our findings also suggest that both NF-κB pathway and lipid peroxidation are implicated in LPS-dependent diminution of PON2.

Original languageEnglish (US)
Pages (from-to)1628-1637
Number of pages10
JournalInternational Journal of Biochemistry and Cell Biology
Volume41
Issue number7
DOIs
StatePublished - Jul 1 2009

Keywords

  • Caco-2 cells
  • Inflammation
  • PON
  • Peroxidation
  • Regulation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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