Hypoxia inducible factor (HIF) modulates endocannabinoid system and NOS activity in human placenta

ABÁN, C, LEGUIZAMÓN G, CELLA M, GARBAGNATI N., RAMIL V., FRANCHI A, FARINA M

Congreso; V Latin American Symposium on Maternal Fetal Interaction & Placenta – SLIMP-LASRI; 2013

Background: Endocannabinoids are lipid mediators that could regulate NOS activity in human placenta. Besides, Hypoxia-inducible Factor (HIF) is a transcription factor that plays an important role in placental physiology. In this study, we investigate the effect of HIF on the endocannabinoid system and NOS activity in human placenta. Methods: Explants obtained from normal placentas were cultured with cobalt chloride (that stabilizes HIF) and/or AM251, cannabinoid receptor antagonist. Expression of the endocannabinoid system was analyzed (RT-PCR and Western Blot). NOS activity was quantified by Bredt & Snyder method. Results: HIF increase NAPE-PLD and decrease FAAH expression, enzymes involved in the main pathways of synthesis and degradation of endocannabinoids. Furthermore, variations in endocannabinoids levels generated by HIF stimulates NOS activity and co-incubation with AM251 revert this effect. Conclusions: HIF modulate the expression of some components of endocannabinoid system suggesting that variations in the endocannabinoid levels could regulate NOS activity in human placenta.