Anandamide oxidative metabolism-induced endoplasmic reticulum stress and apoptosis

• Type: Article in International Scientific Journal
• Date: 2017

Authors

Almada, M (Author) Other; Fonseca, BM (Author) FFUP; Amaral, C (Author) Other; Diniz da Costa, M (Author) Other; Georgina Correia da Silva (Author) FFUP; Teixeira, NA (Author) FFUP

Journal

Title: APOPTOSIS

Vol. 22

Pages: 816-826

ISSN: 13608185

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 17 Citations

Scopus - 19 Citations

Other information

Authenticus ID: P-00M-R1F

DOI: 10.1007/s10495-017-1356-4

Abstract (EN): The Endocannabinoid System (ECS) has been recognized as a crucial player in human reproduction. Changes in the levels of anandamide (AEA), the main endocannabinoid (eCB), negatively affect reproductive events, such as implantation, decidualization and placentation. Cyclooxygenase-2 (COX-2) is a major enzyme expressed in the endometrium and its involvement in female reproductive system has evolved over the last few years. Currently, COX-2 oxidative metabolism is emerging as a key mediator of AEA-induced actions. In this study, we aimed to disclose the mechanisms underlying the effects of AEA in human endometrial stromal cell fate, using a human-derived endometrial cell line (St-T1b). We found that AEA has an anti-proliferative activity through a direct effect on cell cycle progression by inducing G(2)/M arrest. Moreover, high levels of AEA increased COX-2 activity, triggering apoptotic cell death, with loss of mitochondrial membrane potential, induction of caspase -9 and -3/-7 activities, and cleavage of poly (ADP-ribose) polymerase (PARP). In addition, the involvement of intracellular reactive oxygen species (ROS) and endoplasmic reticulum (ER) stress was verified. These effects were prevented by pre-incubation with a selective COX-2 inhibitor. Therefore, we hypothesize that, in response to altered levels of this eCB, COX-2 oxidative metabolism of AEA may deregulate endometrial cell turnover and, consequently, interfere with cellular events crucial for implantation and decidualization, with a negative impact on human fertility.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11