Lipopolysaccharide-induced murine embryonic resorption involves nitric oxide-mediated inhibition of the NADC-dependent 15-hydroxyprostaglandin dehydrogenase

AISEMBERG JULIETA; BARIANI MARIA VICTORIA; VERCELLI, CLAUDIA; WOLFSON MANUEL LUIS; FRANCHI, ANA MARIA

REPRODUCTION

BIOSCIENTIFICA LTD

Lugar: Bristol; Año: 2012 vol. 144 p. 447 - 454

1470-1626

The initial inactivation of prostaglandins (PGs) is mediated by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). PGs are potentmediators of several biological processes, including inflammation and reproduction. In uterus, PGs play a key role in infectioninducedpregnancy loss, in which concentration of this mediator increased. This process is accompanied with the induction of nitricoxide synthase expression and a marked increase in uterine levels of nitric oxide. There is no information concerning nitric oxidecontribution 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 nitricoxide-dependent regulation of this enzyme in a model of lipopolysaccharide (LPS)-induced embryonic resorption. Results show thatLPS decreased HPGD protein expression and augmented PGE synthase activity; therefore, PGE2 levels increased in uterus in thisinflammatory 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 havefound that this enzyme and PGE2 levels are not modulated by peroxynitrite, an oxidant agent derived from nitric oxide. This studysuggests that LPS and nitric oxide promote a decrease in the ability of the uterus for PG catabolism during bacterially triggeredpregnancy loss in mice.