Early methyl donor deficiency produces severe gastritis in mothers and offspring throughN‐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; PPPPPPN-homocysteinylation, marked inflammation, and apoptosis, despite activation of repair machinery.—Bossenmeyer-Pourié, C., Pourié, G., Koziel, V., Helle, D., Jeannesson, E., Guéant, J.-L., and Beck, B. Early methyl donor deficiency produces severe gastritis in mothers and offspring through N-homocysteinylation of cytoskeleton proteins, cellular stress, and inflammation. FASEB J. 27, 2185–2197 (2013). www.fasebj.org