title: Early methyl donor deficiency produces severe gastritis in mothers and offspring through N-homocysteinylation of cytoskeleton proteins, cellular stress, and inflammation.
abstract: We examined the gastric mucosa structure and inflammatory status in control well-nourished Wistar dams and in Wistar dams deprived of choline, folate, and vitamin B12 during gestation and suckling periods, and in their offspring just before birth and at weaning. In this model of methyl donor deficiency (MDD), structural protein (E-cadherin and actin) N-homocysteinylation was measured through immunoprecipitation and proximity ligation assays. Cellular stress, inflammation, and apoptosis were estimated by the analysis of the NF-κB pathway, and the expression of superoxide dismutase, cyclooxygenase-2, tumor necrosis factor α, caspases 3 and 9, and TUNEL assay. Aberrant gastric mucosa formation and signs of surface layer erosion were detected in MDD fetuses and weanlings. E-cadherin and actin were N-homocysteinylated (+215 and +249% vs. controls, respectively; P<0.001). Expression of β-catenin staining drastically decreased (-98%; P<0.01). NF-κB pathway was activated (+124%; P<0.01). Expressions of all inflammatory factors (+70%; P<0.01), superoxide dismutase (+55%; P<0.01), and caspases (+104%; P<0.01) were markedly increased. These changes were also observed in dams, to a lesser extent. Early MDD induced gastric mucosa injury similar to atrophic gastritis through structural protein N-homocysteinylation, marked inflammation, and apoptosis, despite activation of repair machinery.
authors: Institut National de la Santé et de la Recherche Médicale, U954, Nutrition, Génétique et Exposition aux Risques Environnementaux, Vandoeuvre, France.
authors: Carine
authors: C
authors: Bossenmeyer-Pourié
authors: Grégory
authors: G
authors: Pourié
authors: Violette
authors: V
authors: Koziel
authors: Deborah
authors: D
authors: Helle
authors: Elise
authors: E
authors: Jeannesson
authors: Jean-Louis
authors: JL
authors: Guéant
authors: Bernard
authors: B
authors: Beck
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D000833:Animals, Suckling; D015820:Cadherins / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D005260:Female; D005333:Fetus; D005756:Gastritis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D006710:Homocysteine / Q000378:metabolism*; D007249:Inflammation / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D008745:Methylation; D009035:Mothers; D018384:Oxidative Stress / Q000502:physiology*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000502:physiology
chemical_list: D015820:Cadherins; D003598:Cytoskeletal Proteins; D006710:Homocysteine
keywords: E-cadherin; NF-κB pathway; actin; apoptosis; oxidative stress