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Anandamide and decidual remodelling: COX-2 oxidative metabolism as a key regulator

Title
Anandamide and decidual remodelling: COX-2 oxidative metabolism as a key regulator
Type
Article in International Scientific Journal
Year
2015
Authors
Almada, M
(Author)
Other
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Piscitelli, F
(Author)
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Fonseca, BM
(Author)
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Di Marzo, V
(Author)
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Georgina Correia da Silva
(Author)
FFUP
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Journal
Vol. 1851
Pages: 1473-1481
ISSN: 1388-1981
Publisher: Elsevier
Scientific classification
FOS: Natural sciences > Biological sciences
Other information
Authenticus ID: P-00G-NBB
Abstract (EN): Recently, endocannabinoids have emerged as signalling mediators in reproduction. It is widely accepted that anandamide (AEA) levels must be tightly regulated, and that a disturbance in AEA levels may impact decidual stability and regression. We have previously characterized the endocannabinoid machinery in rat decidual tissue and reported the pro-apoptotic action of AEA on rat decidual cells. Cyclooxygenase-2 (COX-2) is an inducible enzyme that plays a crucial role in early pregnancy, and is also a key modulator in the crosstalk between endocannabinoids and prostaglandins. On the other hand, AEA-oxidative metabolism by COX-2 is not merely a mean to inactivate its action, but it yields the formation of a new class of mediators, named prostaglandin-ethanolamides, or prostamides. In this study we found that AEA-induced apoptosis in decidual cells involves COX-2 metabolic pathway. AEA induced COX-2 expression through p38 MAPK, resulting in the formation of prostamide E2 (PME2). Our findings also suggest that AEA-induced effect is associated with NF-kappa B activation. Finally, we describe the involvement of PME2 in the induction of the intrinsic apoptotic pathway in rat decidual cells. Altogether, our findings highlight the role of COX-2 as a gatekeeper in the uterine environment and clarify the impact of the deregulation of AEA levels on the decidual remodelling process.
Language: English
Type (Professor's evaluation): Scientific
No. of pages: 9
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