TY - JOUR
T1 - Comparative expression analysis reveals differences in the regulation of intestinal paraoxonase family members
AU - Precourt, Louis Philippe
AU - Seidman, Ernest
AU - Delvin, Edgard
AU - Amre, Devendra
AU - Deslandres, Colette
AU - Dominguez, Michel
AU - Sinnett, Daniel
AU - Levy, Emile
N1 - Funding Information:
The current work was supported by research grant from the Crohn's and Colitis Foundation of Canada (CCFC). The authors thank Schohraya Spahis, François Leblond, Geneviève Lalonde and Sanchez Garcia, Maria del Rocio for their expert technical assistance.
PY - 2009/7
Y1 - 2009/7
N2 - 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.
AB - 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.
KW - Caco-2 cells
KW - Inflammation
KW - PON
KW - Peroxidation
KW - Regulation
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U2 - 10.1016/j.biocel.2009.02.013
DO - 10.1016/j.biocel.2009.02.013
M3 - Article
C2 - 19401157
AN - SCOPUS:63249089804
SN - 1357-2725
VL - 41
SP - 1628
EP - 1637
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
IS - 7
ER -