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The endocannabinoid anandamide induces apoptosis in cytotrophoblast cells: involvement of both mitochondrial and death receptor pathways.
Placenta. 2015 Jan; 36(1):69-76.P

Abstract

INTRODUCTION

A balanced proliferation, apoptosis and differentiation in trophoblast cells of the human placenta is crucial for a proper placental development. Alteration in trophoblast apoptosis and differentiation are associated with gestational-related complications, such as preeclampsia, intrauterine growth restriction or miscarriages. The endocannabinoids (eCBs) have been recognized as new interveners in pregnancy events such as implantation and decidualization. However, their importance in placentation is poorly understood. We hypothesise that these novel lipid mediators may intervene in cytotrophoblast apoptosis and, concomitantly, have a role during placental development.

METHODS

primary human cytotrophoblasts (hCTs) and the human trophoblast-like choriocarcinoma cell line BeWo cells were exposed to Anandamide (AEA). It was investigated the cellular pathways involved in cell death, by the assessment of cell morphology, caspases activity, mitochondrial membrane potential (Δψm), reactive oxygen/nitrogen species (ROS/RNS) and western blot of cleaved Poly (ADP-ribose) polymerase 1 (PARP-1), truncated Bid (t-Bid) and IκB-α.

RESULTS

AEA decreased hCTs viability and induced morphological features of apoptosis (chromatin condensation and fragmentation), caspase-3/7 activation and PARP-1 cleavage. In BeWo, AEA also increased the activities of caspase-3/7 and 9, induced loss in Δψm and production of ROS/RNS. These effects were reversed by either CB1 or CB2 antagonists, whereas the increase in caspase-3/7 activity was only reversed with CB2 blockage. AEA-treated cells showed increased caspase-8 activation and formation of t-Bid, suggesting the interplay between intrinsic and extrinsic apoptotic pathways. AEA also increased IκB-α expression, a NF-κB regulatory protein.

CONCLUSION

Our results highlight the importance of eCBs in cytotrophoblast cell apoptosis and indicate that a crosstalk between intrinsic and extrinsic apoptotic pathways is involved in AEA-induced effects.

Authors+Show Affiliations

Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; Instituto de Biologia Molecular e Celular da Universidade do Porto (IBMC), Porto, Portugal.Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; Instituto de Biologia Molecular e Celular da Universidade do Porto (IBMC), Porto, Portugal.Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; Instituto de Biologia Molecular e Celular da Universidade do Porto (IBMC), Porto, Portugal.Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia, Universidade do Porto, Porto, Portugal; Instituto de Biologia Molecular e Celular da Universidade do Porto (IBMC), Porto, Portugal. Electronic address: george@ff.up.pt.

Pub Type(s)

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

Language

eng

PubMed ID

25465706

Citation

Costa, M A., et al. "The Endocannabinoid Anandamide Induces Apoptosis in Cytotrophoblast Cells: Involvement of Both Mitochondrial and Death Receptor Pathways." Placenta, vol. 36, no. 1, 2015, pp. 69-76.
Costa MA, Fonseca BM, Teixeira NA, et al. The endocannabinoid anandamide induces apoptosis in cytotrophoblast cells: involvement of both mitochondrial and death receptor pathways. Placenta. 2015;36(1):69-76.
Costa, M. A., Fonseca, B. M., Teixeira, N. A., & Correia-da-Silva, G. (2015). The endocannabinoid anandamide induces apoptosis in cytotrophoblast cells: involvement of both mitochondrial and death receptor pathways. Placenta, 36(1), 69-76. https://doi.org/10.1016/j.placenta.2014.10.011
Costa MA, et al. The Endocannabinoid Anandamide Induces Apoptosis in Cytotrophoblast Cells: Involvement of Both Mitochondrial and Death Receptor Pathways. Placenta. 2015;36(1):69-76. PubMed PMID: 25465706.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The endocannabinoid anandamide induces apoptosis in cytotrophoblast cells: involvement of both mitochondrial and death receptor pathways. AU - Costa,M A, AU - Fonseca,B M, AU - Teixeira,N A, AU - Correia-da-Silva,G, Y1 - 2014/11/01/ PY - 2014/09/12/received PY - 2014/10/15/revised PY - 2014/10/21/accepted PY - 2014/12/4/entrez PY - 2014/12/4/pubmed PY - 2015/8/22/medline KW - Anandamide KW - Apoptosis KW - Cytotrophoblasts KW - Endocannabinoid signalling KW - Placenta SP - 69 EP - 76 JF - Placenta JO - Placenta VL - 36 IS - 1 N2 - INTRODUCTION: A balanced proliferation, apoptosis and differentiation in trophoblast cells of the human placenta is crucial for a proper placental development. Alteration in trophoblast apoptosis and differentiation are associated with gestational-related complications, such as preeclampsia, intrauterine growth restriction or miscarriages. The endocannabinoids (eCBs) have been recognized as new interveners in pregnancy events such as implantation and decidualization. However, their importance in placentation is poorly understood. We hypothesise that these novel lipid mediators may intervene in cytotrophoblast apoptosis and, concomitantly, have a role during placental development. METHODS: primary human cytotrophoblasts (hCTs) and the human trophoblast-like choriocarcinoma cell line BeWo cells were exposed to Anandamide (AEA). It was investigated the cellular pathways involved in cell death, by the assessment of cell morphology, caspases activity, mitochondrial membrane potential (Δψm), reactive oxygen/nitrogen species (ROS/RNS) and western blot of cleaved Poly (ADP-ribose) polymerase 1 (PARP-1), truncated Bid (t-Bid) and IκB-α. RESULTS: AEA decreased hCTs viability and induced morphological features of apoptosis (chromatin condensation and fragmentation), caspase-3/7 activation and PARP-1 cleavage. In BeWo, AEA also increased the activities of caspase-3/7 and 9, induced loss in Δψm and production of ROS/RNS. These effects were reversed by either CB1 or CB2 antagonists, whereas the increase in caspase-3/7 activity was only reversed with CB2 blockage. AEA-treated cells showed increased caspase-8 activation and formation of t-Bid, suggesting the interplay between intrinsic and extrinsic apoptotic pathways. AEA also increased IκB-α expression, a NF-κB regulatory protein. CONCLUSION: Our results highlight the importance of eCBs in cytotrophoblast cell apoptosis and indicate that a crosstalk between intrinsic and extrinsic apoptotic pathways is involved in AEA-induced effects. SN - 1532-3102 UR - https://www.unboundmedicine.com/medline/citation/25465706/The_endocannabinoid_anandamide_induces_apoptosis_in_cytotrophoblast_cells:_involvement_of_both_mitochondrial_and_death_receptor_pathways_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0143-4004(14)00823-6 DB - PRIME DP - Unbound Medicine ER -