title: Lipopolysaccharide-induced murine embryonic resorption involves nitric oxide-mediated inhibition of the NAD+-dependent 15-hydroxyprostaglandin dehydrogenase.
abstract: The initial inactivation of prostaglandins (PGs) is mediated by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). PGs are potent mediators of several biological processes, including inflammation and reproduction. In uterus, PGs play a key role in infection-induced pregnancy loss, in which concentration of this mediator increased. This process is accompanied with the induction of nitric oxide synthase expression and a marked increase in uterine levels of nitric oxide. There is no information concerning nitric oxide contribution to potential changes in PG catabolism, but experimental evidence suggests that nitric oxide modulates PG pathways. The specific objectives of the study were to evaluate the protein expression of HPGD (15-PGDH) and to characterize the nitric oxide-dependent regulation of this enzyme in a model of lipopolysaccharide (LPS)-induced embryonic resorption. Results show that LPS decreased HPGD protein expression and augmented PGE synthase activity; therefore, PGE₂ levels increased in uterus in this inflammatory condition. Just as LPS, the treatment with a nitric oxide donor diminished HPGD protein expression in uterine tissue. In contrast, the inhibition of nitric oxide synthesis both in control and in LPS-treated mice increased 15-PGDH levels. Also, we have found that this enzyme and PGE₂ levels are not modulated by peroxynitrite, an oxidant agent derived from nitric oxide. This study suggests that LPS and nitric oxide promote a decrease in the ability of the uterus for PG catabolism during bacterially triggered pregnancy loss in mice.
authors: Centro de Estudios Farmacológicos y Botánicos (CEFYBO, CONICET-UBA), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina. jaisemberg@yahoo.com.ar
authors: Julieta
authors: J
authors: Aisemberg
authors: María V
authors: MV
authors: Bariani
authors: Claudia A
authors: CA
authors: Vercelli
authors: Manuel L
authors: ML
authors: Wolfson
authors: Ana M
authors: AM
authors: Franchi
mesh_terms: D000818:Animals; D015232:Dinoprostone / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D020964:Embryo Loss / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004927:Escherichia coli Infections / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D005260:Female; D006911:Hydroxyprostaglandin Dehydrogenases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008070:Lipopolysaccharides; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000201:enzymology / Q000276:immunology / Q000378:metabolism; D000071876:Prostaglandin-E Synthases; D011897:Random Allocation; D015854:Up-Regulation / Q000187:drug effects; D014599:Uterus / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D006911:Hydroxyprostaglandin Dehydrogenases; C035859:15-hydroxyprostaglandin dehydrogenase; D019001:Nitric Oxide Synthase; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; D015232:Dinoprostone