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Modulation of the human paraoxonase gene family members by various effectors in Caco‐2 cells
Author(s) -
Précourt LouisPhilippe,
Delvin Edgard,
Amre Devendra,
Sinnett Daniel,
Seidman Ernest,
Levy Emile
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1189.9
Subject(s) - paraoxonase , pon1 , gene , antioxidant , biology , gene expression , oxidative stress , chemistry , biochemistry , microbiology and biotechnology , genotype
The human paraoxonase (PON) gene family is composed of three members (PON1, PON2, PON3) aligned next to each other on chromosome 7. They are highly conserved in mammals, display similarities in their structural properties (~65% identity atthe amino acid level) and seem to play an important part in oxidative stress. Recently, PONs have been detected in the gastrointestinal tract, but their physiological roles and regulation remain obscure. Our objective was to examine the modulation of PON1, PON2 and PON3 in the Caco‐2 cell line. Fe 2+ ‐ascorbate‐mediated lipid peroxidation promoted MDA formation without affecting sucrase activity, transepithelial resistance, DNA and protein content, as well as cell viability. The addition of the oxygen radical‐generating system reduced the gene expression of PON1, PON2 and PON3. Pre‐incubation with the antioxidant BHT or Trolox restrained the production of MDA and the inhibitory effect on PON mRNA levels. Similarly, the administration of CAPE, an inhibitor of NF‐kB activity, reversed the negative influence of inflammatory agents, including LPS, TNF‐α and INF‐γ. Rosiglitazone and DHA enhanced the gene expression of PON1 and PON3 without any influence on PON2 mRNA levels. Our data indicate that various effectors may impact on the gene expression of PON1, PON2 and PON3, sometimes with a distinct modulation. Supported by Crohn's and Colitis Foundation of Canada.