title: Biological role, protein expression, subcellular localization, and oxidative stress response of paraoxonase 2 in the intestine of humans and rats.
abstract: Oxidative stress is a cardinal manifestation of various intestinal disorders. However, very little knowledge is available on the intestine's inherent defense mechanisms against free radicals. This study was designed to determine the protein expression, subcellular localization and oxidative stress response of paraoxonase 2 (PON2), a member of a powerful antioxidant family in human and rat intestine. Biochemical and ultrastructural experiments all showed a substantial expression of PON2 in human and rat intestine. Western blot analysis disclosed higher levels of PON2 in the jejunum than in the duodenum, ileum, and colon. Cell fractionation revealed a predominant PON2 association with microsomes and lysosomes in the human jejunum, which differed from that in rats. PON2 was detected in the intestine as early as week 15 of gestation and was significantly increased by week 20. Iron ascorbate-mediated lipid peroxidation induced a marked decrease in PON2 expression in intestinal specimens coincidental to an abundant rise in malondialdehyde (MDA). On the other hand, preincubation with potent antioxidants, such as butylated hydroxytoluene, Trolox, and N-acetylcysteine, prevented iron-ascorbate-generating PON2 reduction in parallel with MDA suppression. Finally, the preincubation of permeabilized Caco-2 cells with purified PON2 led to a protection against iron-ascorbate-induced lipid peroxidation. These observations demonstrate that the human intestine is preferentially endowed with a marked PON2 expression compared with the rat intestine and this expression shows a developmental and intracellular pattern of distribution. Furthermore, our observations suggest PON2 protective effects against prooxidant stimuli in the small intestine.
authors.affiliation: Department of Nutrition, Université de Montréal, Research Centre, CHU Sainte Justine, Montréal, Québec, Canada. emile.levy@recherche-ste-justine.qc.ca
authors.forename: Emile
authors.initials: E
authors.lastname: Levy
authors.forename: Karine
authors.initials: K
authors.lastname: Trudel
authors.forename: Moise
authors.initials: M
authors.lastname: Bendayan
authors.forename: Ernest
authors.initials: E
authors.lastname: Seidman
authors.forename: Edgard
authors.initials: E
authors.lastname: Delvin
authors.forename: Mounib
authors.initials: M
authors.lastname: Elchebly
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Lavoie
authors.forename: Louis-Philippe
authors.initials: LP
authors.lastname: Precourt
authors.forename: Devendra
authors.initials: D
authors.lastname: Amre
authors.forename: Daniel
authors.initials: D
authors.lastname: Sinnett
mesh_terms: D000818:Animals; D043303:Aryldialkylphosphatase / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008875:Middle Aged; D018384:Oxidative Stress / Q000502:physiology*; D051381:Rats; D013045:Species Specificity; D013347:Subcellular Fractions / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D043303:Aryldialkylphosphatase; C000605116:paraoxonase 2, rat