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2-arachidonoylglycerol effects in cytotrophoblasts: metabolic enzymes expression and apoptosis in BeWo cells.
Reproduction. 2014 Mar; 147(3):301-11.R

Abstract

The major endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) is a member of the endocannabinoid system (ECS) that participates in cell proliferation and apoptosis, important events for the homoeostasis of biological systems. The formation of placenta is one of the most important stages of pregnancy and its development requires highly regulated proliferation, differentiation and apoptosis of trophoblasts. Anomalies in these processes are associated with gestational pathologies. In this work, we aimed to study the involvement of 2-AG in cytotrophoblast cell turnover. We found that 2-AG biosynthetic (diacylglycerol lipase A) and degradative (monoacylglycerol lipase) enzymes are expressed in human cytotrophoblasts and in BeWo cells. We also found that 2-AG induces a decrease in cell viability in a time- and concentration-dependent manner and exerts antiproliferative effects. The loss of cell viability induced by a 48-h treatment with 2-AG (10 μM) was accompanied by chromatin fragmentation and condensation, morphological features of apoptosis. Additionally, 2-AG induced an increase in caspase 3/7 and 9 activities, a loss of mitochondrial membrane potential (Δψm) and an increase in reactive oxygen species (ROS)/reactive nitrogen species (RNS) generation, suggesting the activation of the mitochondrial pathway. Moreover, whereas Δψm loss and ROS/RNS generation were significantly attenuated by the antagonists of both the cannabinoid receptors 1 and 2 (CB1 and CB2), the increase in caspase 3/7 and 9 activities and loss of cell viability were reversed only by the antagonist of CB2 receptor; the blockage of the eCB membrane transporter and the depletion of cholesterol failed to reverse the effects of 2-AG. Therefore, this work supports the importance of cannabinoid signalling during cytotrophoblast cell turnover and that its deregulation may be responsible for altered placental development and poor pregnancy outcomes.

Authors+Show Affiliations

Laboratório de Bioquímica, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira n.° 228, 4050-313 Porto, Portugal.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24324206

Citation

Costa, M A., et al. "2-arachidonoylglycerol Effects in Cytotrophoblasts: Metabolic Enzymes Expression and Apoptosis in BeWo Cells." Reproduction (Cambridge, England), vol. 147, no. 3, 2014, pp. 301-11.
Costa MA, Fonseca BM, Keating E, et al. 2-arachidonoylglycerol effects in cytotrophoblasts: metabolic enzymes expression and apoptosis in BeWo cells. Reproduction. 2014;147(3):301-11.
Costa, M. A., Fonseca, B. M., Keating, E., Teixeira, N. A., & Correia-da-Silva, G. (2014). 2-arachidonoylglycerol effects in cytotrophoblasts: metabolic enzymes expression and apoptosis in BeWo cells. Reproduction (Cambridge, England), 147(3), 301-11. https://doi.org/10.1530/REP-13-0563
Costa MA, et al. 2-arachidonoylglycerol Effects in Cytotrophoblasts: Metabolic Enzymes Expression and Apoptosis in BeWo Cells. Reproduction. 2014;147(3):301-11. PubMed PMID: 24324206.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 2-arachidonoylglycerol effects in cytotrophoblasts: metabolic enzymes expression and apoptosis in BeWo cells. AU - Costa,M A, AU - Fonseca,B M, AU - Keating,E, AU - Teixeira,N A, AU - Correia-da-Silva,G, Y1 - 2014/02/03/ PY - 2013/12/11/entrez PY - 2013/12/11/pubmed PY - 2014/10/22/medline SP - 301 EP - 11 JF - Reproduction (Cambridge, England) JO - Reproduction VL - 147 IS - 3 N2 - The major endocannabinoid (eCB) 2-arachidonoylglycerol (2-AG) is a member of the endocannabinoid system (ECS) that participates in cell proliferation and apoptosis, important events for the homoeostasis of biological systems. The formation of placenta is one of the most important stages of pregnancy and its development requires highly regulated proliferation, differentiation and apoptosis of trophoblasts. Anomalies in these processes are associated with gestational pathologies. In this work, we aimed to study the involvement of 2-AG in cytotrophoblast cell turnover. We found that 2-AG biosynthetic (diacylglycerol lipase A) and degradative (monoacylglycerol lipase) enzymes are expressed in human cytotrophoblasts and in BeWo cells. We also found that 2-AG induces a decrease in cell viability in a time- and concentration-dependent manner and exerts antiproliferative effects. The loss of cell viability induced by a 48-h treatment with 2-AG (10 μM) was accompanied by chromatin fragmentation and condensation, morphological features of apoptosis. Additionally, 2-AG induced an increase in caspase 3/7 and 9 activities, a loss of mitochondrial membrane potential (Δψm) and an increase in reactive oxygen species (ROS)/reactive nitrogen species (RNS) generation, suggesting the activation of the mitochondrial pathway. Moreover, whereas Δψm loss and ROS/RNS generation were significantly attenuated by the antagonists of both the cannabinoid receptors 1 and 2 (CB1 and CB2), the increase in caspase 3/7 and 9 activities and loss of cell viability were reversed only by the antagonist of CB2 receptor; the blockage of the eCB membrane transporter and the depletion of cholesterol failed to reverse the effects of 2-AG. Therefore, this work supports the importance of cannabinoid signalling during cytotrophoblast cell turnover and that its deregulation may be responsible for altered placental development and poor pregnancy outcomes. SN - 1741-7899 UR - https://www.unboundmedicine.com/medline/citation/24324206/2_arachidonoylglycerol_effects_in_cytotrophoblasts:_metabolic_enzymes_expression_and_apoptosis_in_BeWo_cells_ L2 - https://rep.bioscientifica.com/doi/10.1530/REP-13-0563 DB - PRIME DP - Unbound Medicine ER -