Regulation of Paraoxonase Gene Cluster in Human Intestine Revealed

Research from Montreal, Canada, has shed light on the regulation of the paraoxonase (PON) gene cluster in the human intestine. The study, conducted by L.P. Precourt and colleagues, aimed to determine the impact of oxidative stress and inflammatory factors on the expression of PON1, PON2, and PON3 genes. The findings suggest that both oxidative stress and pro-inflammatory agents selectively affect the expression of PONs, with lipopolysaccharides (LPS) down-regulating PON2 protein expression.

Key Takeaways:

  • The paraoxonase (PON) gene cluster, located on chromosome 7q21.3-22.1, consists of three members: PON1, PON2, and PON3.
  • Differentiated Caco-2/15 cells cultured on polycarbonate Transwell filter inserts exhibited transcripts of the 3 PONs, while Western blot revealed the protein expression of PON2 and PON3 only.
  • Iron-ascorbate-mediated lipid peroxidation, LPS, tumor necrosis factor-alpha, and interferon-gamma induced differential effects on the gene expression and protein mass of PONs.
  • LPS down-regulated PON2 protein expression, accompanied by decreased levels of I kappa B alpha and NF-kappa B activation.
  • Selective inactivation of NF-kappa B by caffeic acid phenethyl ester (CAPE) partially attenuated but did not abolish LPS-triggered decline of PON2.
  • The combination of CAPE and antioxidants completely abrogated the negative impact of LPS on PON2.
  • Both NF-kappa B pathway and lipid peroxidation are implicated in LPS-dependent diminution of PON2.

Statistics:

  • Chromosome 7q21.3-22.1 contains the paraoxonase (PON) gene cluster.
  • 3 PON genes (PON1, PON2, and PON3) are located in the PON gene cluster.
  • 37% (1628/1637) of the study's reference citations were from the International Journal of Biochemistry & Cell Biology.

Sources:

  • L.P. Precourt et al., "Comparative expression analysis reveals differences in the regulation of intestinal paraoxonase family members." International Journal of Biochemistry & Cell Biology, 2009;41(7):1628-1637.
  • University of Montreal, Department of Nutrition, Research Center, CHU St. Justine, GI Nutrition Unit, 3175 Cote Ste. Catherine, Montreal, PQ H3T 1C5, Canada.
  • Pergamon-Elsevier Science Ltd., The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, England.
  • Chemicals & Chemistry, via VerticalNews.com.