title: Comparative expression analysis reveals differences in the regulation of intestinal paraoxonase family members.
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-alpha and interferon-gamma 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 IkappaBalpha, the inhibitor of the proinflammatory transcription factor nuclear factor-kappa B (NF-kappaB). Selective inactivation of NF-kappaB 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-kappaB pathway and lipid peroxidation are implicated in LPS-dependent diminution of PON2.
authors.affiliation: Department of Nutrition, Université de Montréal, Research Centre, CHU Sainte Justine, 3175 Côte Ste-Catherine, Montréal, Québec, Canada.
authors.forename: Louis-Philippe
authors.initials: LP
authors.lastname: Precourt
authors.forename: Ernest
authors.initials: E
authors.lastname: Seidman
authors.forename: Edgard
authors.initials: E
authors.lastname: Delvin
authors.forename: Devendra
authors.initials: D
authors.lastname: Amre
authors.forename: Colette
authors.initials: C
authors.lastname: Deslandres
authors.forename: Michel
authors.initials: M
authors.lastname: Dominguez
authors.forename: Daniel
authors.initials: D
authors.lastname: Sinnett
authors.forename: Emile
authors.initials: E
authors.lastname: Levy
mesh_terms: D043303:Aryldialkylphosphatase / Q000235:genetics* / Q000378:metabolism*; D001205:Ascorbic Acid / Q000494:pharmacology; D018938:Caco-2 Cells; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D007422:Intestines / Q000201:enzymology*; D007501:Iron / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606204:NFKBIA protein, human; D045162:Thiazolidinediones; D014409:Tumor Necrosis Factor-alpha; D000077154:Rosiglitazone; D000072000:NF-KappaB Inhibitor alpha; D007371:Interferon-gamma; D007501:Iron; D043303:Aryldialkylphosphatase; D001205:Ascorbic Acid