Journal
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Volume 303, Issue 5, Pages G623-G634Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00039.2012
Keywords
paraoxonase; small intestine; oxidative stress; inflammation; lipid peroxidation
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Funding
- Crohn's and Colitis Foundation of Canada
- Canadian Institute of Health Research [CTP-82942]
- J. A. de Seve Research Chair in Nutrition
- Fonds de la Recherche en Sante du Quebec Scholarship Award
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Precourt LP, Marcil V, Ntimbane T, Taha R, Lavoie JC, Delvin E, Seidman EG, Beaulieu JF, Levy E. Antioxidative properties of paraoxonase 2 in intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 303: G623-G634, 2012. First published June 28, 2012; doi:10.1152/ajpgi.00039.2012.-Paraoxonase (PON) family members seem central to a wide variety of human illnesses, but appreciation of their antioxidative function in the gastrointestinal tract is in its infancy. The major objective of the present work is to highlight the role of the ubiquitously expressed PON2 in the small intestine. With use of pLKO lentiviral vector containing short hairpin RNA (shRNA) lentivirus, PON2 expression was knocked down in intestinal Caco2/15 cells, where antioxidative status, lipid peroxidation, and degree of inflammation were evaluated. As a consequence of PON2 inactivation in the epithelial cells, we observed 1) imbalanced primary and secondary antioxidative responses, characterized by increased superoxide dismutases and decreased catalase, 2) high concentrations of H2O2 and malondialdehyde, along with low glutathione-to-glutathione disulfide ratio, 3) upregulation of TNF-alpha, IL-6, and monocyte chemoattractant protein-1 gene expression after induction of oxidative stress, and 4) raised level of the activation of transcription factor NF-kappa B, which was likely implicated in exacerbation of the inflammatory activation. These results suggest that PON2 is involved in the antioxidative and anti-inflammatory response in intestinal epithelial cells.
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