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The endocannabinoid anandamide induces apoptosis of rat decidual cells through a mechanism involving ceramide synthesis and p38 MAPK activation.
Apoptosis. 2013 Dec; 18(12):1526-35.A

Abstract

Anandamide (AEA) belongs to an endogenous family of lipid messengers, called endocannabinoids (ECs), which exert pharmacological effects by binding to selective membrane receptors, the CB1 and CB2 receptors. Increasing evidence suggests that AEA is involved in the regulation of a variety of cell signalling pathways both in experimental models and humans. We have previously demonstrated that ECs machinery operates in decidual cells and found that AEA, the principal EC, induced apoptosis in decidual cells through CB1. Here, we investigated in rat primary decidual cells the signal transduction pathways activated upon AEA binding to CB1. We found that AEA induces a significant increase in the level of intracellular ceramide. These effects were reversed by inhibiting CB1 receptor activation with AM251. The ceramide analogue, C6-ceramide, induced a decrease in decidual cell viability and of p38 MAPK phosphorylation. Additionally, the pharmacologic inhibition of de novo ceramide biosynthesis with L-cycloserine and fumonisin B reduced the AEA-effects on cell viability and p38 MAPK phosphorylation. Furthermore, AEA and C6-ceramide induced a drop in ΔΨm, an increase in ROS production and caspase-3/-7 activation, effects partially reverted by inhibitors of ceramide synthesis and of p38 MAPK. Taken together, we showed that AEA induces a reduction in decidual cell viability by a mechanism involving CB1 activation, which results in ceramide synthesis de novo and p38 phosphorylation, followed by mitochondrial stress and ROS production, leading to apoptosis.

Authors+Show Affiliations

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

Pub Type(s)

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

Language

eng

PubMed ID

24048885

Citation

Fonseca, B M., et al. "The Endocannabinoid Anandamide Induces Apoptosis of Rat Decidual Cells Through a Mechanism Involving Ceramide Synthesis and P38 MAPK Activation." Apoptosis : an International Journal On Programmed Cell Death, vol. 18, no. 12, 2013, pp. 1526-35.
Fonseca BM, Correia-da-Silva G, Teixeira NA. The endocannabinoid anandamide induces apoptosis of rat decidual cells through a mechanism involving ceramide synthesis and p38 MAPK activation. Apoptosis. 2013;18(12):1526-35.
Fonseca, B. M., Correia-da-Silva, G., & Teixeira, N. A. (2013). The endocannabinoid anandamide induces apoptosis of rat decidual cells through a mechanism involving ceramide synthesis and p38 MAPK activation. Apoptosis : an International Journal On Programmed Cell Death, 18(12), 1526-35. https://doi.org/10.1007/s10495-013-0892-9
Fonseca BM, Correia-da-Silva G, Teixeira NA. The Endocannabinoid Anandamide Induces Apoptosis of Rat Decidual Cells Through a Mechanism Involving Ceramide Synthesis and P38 MAPK Activation. Apoptosis. 2013;18(12):1526-35. PubMed PMID: 24048885.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The endocannabinoid anandamide induces apoptosis of rat decidual cells through a mechanism involving ceramide synthesis and p38 MAPK activation. AU - Fonseca,B M, AU - Correia-da-Silva,G, AU - Teixeira,N A, PY - 2013/9/20/entrez PY - 2013/9/21/pubmed PY - 2014/7/16/medline SP - 1526 EP - 35 JF - Apoptosis : an international journal on programmed cell death JO - Apoptosis VL - 18 IS - 12 N2 - Anandamide (AEA) belongs to an endogenous family of lipid messengers, called endocannabinoids (ECs), which exert pharmacological effects by binding to selective membrane receptors, the CB1 and CB2 receptors. Increasing evidence suggests that AEA is involved in the regulation of a variety of cell signalling pathways both in experimental models and humans. We have previously demonstrated that ECs machinery operates in decidual cells and found that AEA, the principal EC, induced apoptosis in decidual cells through CB1. Here, we investigated in rat primary decidual cells the signal transduction pathways activated upon AEA binding to CB1. We found that AEA induces a significant increase in the level of intracellular ceramide. These effects were reversed by inhibiting CB1 receptor activation with AM251. The ceramide analogue, C6-ceramide, induced a decrease in decidual cell viability and of p38 MAPK phosphorylation. Additionally, the pharmacologic inhibition of de novo ceramide biosynthesis with L-cycloserine and fumonisin B reduced the AEA-effects on cell viability and p38 MAPK phosphorylation. Furthermore, AEA and C6-ceramide induced a drop in ΔΨm, an increase in ROS production and caspase-3/-7 activation, effects partially reverted by inhibitors of ceramide synthesis and of p38 MAPK. Taken together, we showed that AEA induces a reduction in decidual cell viability by a mechanism involving CB1 activation, which results in ceramide synthesis de novo and p38 phosphorylation, followed by mitochondrial stress and ROS production, leading to apoptosis. SN - 1573-675X UR - https://www.unboundmedicine.com/medline/citation/24048885/The_endocannabinoid_anandamide_induces_apoptosis_of_rat_decidual_cells_through_a_mechanism_involving_ceramide_synthesis_and_p38_MAPK_activation_ L2 - https://doi.org/10.1007/s10495-013-0892-9 DB - PRIME DP - Unbound Medicine ER -