Title |
Anandamide oxidative metabolism-induced endoplasmic reticulum stress and apoptosis
|
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Published in |
Apoptosis, February 2017
|
DOI | 10.1007/s10495-017-1356-4 |
Pubmed ID | |
Authors |
M. Almada, B. M. Fonseca, C. Amaral, M. Diniz-da-Costa, G. Correia-da-Silva, N. Teixeira |
Abstract |
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 G2/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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 23 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 4 | 17% |
Researcher | 3 | 13% |
Student > Master | 3 | 13% |
Student > Bachelor | 2 | 9% |
Professor | 2 | 9% |
Other | 3 | 13% |
Unknown | 6 | 26% |
Readers by discipline | Count | As % |
---|---|---|
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Biochemistry, Genetics and Molecular Biology | 3 | 13% |
Medicine and Dentistry | 3 | 13% |
Neuroscience | 2 | 9% |
Other | 1 | 4% |
Unknown | 8 | 35% |