Impact of tetrahydrocannabinol on the endocannabinoid 2-arachidonoylglycerol metabolism: ABHD6 and ABHD12 as novel players in human placenta

• Tipo: Artigo em Revista Científica Internacional
• Data: 2020

Autores

Maia, J (Autor) Outra; Fonseca, BM (Autor) Outra; Cunha, SC (Autor) Outra; Braga, J (Autor) Outra; Goncalves, D (Autor) Outra; Teixeira, N (Autor) Outra; Georgina Correia da Silva (Autor) FFUP

Revista

Título: Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids

Vol. 1865

ISSN: 1388-1981

Editora: Elsevier

Indexação

ISI Web of Knowledge - 0 Citações

Scopus - 1 Citação

Outras Informações

ID Authenticus: P-00S-NGP

DOI: 10.1016/j.bbalip.2020.158807

Abstract (EN): Cannabis use has been increasing worldwide for recreational and medical purposes. Consumption by pregnant women is associated with disturbances in pregnancy outcome, such as low birth weight, prematurity and intrauterine growth retardation, though the underlying biochemical mechanisms are unknown. The endocannabinoid system is involved in several reproductive events and the disruption of its homeostasis by Delta(9)-tetrahydrocannabinol (THC), the main psychoactive cannabinoid, may lead to a negative gestational outcome. In human placenta, THC impairs the levels of the endocannabinoid anandamide (AEA). The other major endocannabinoid, 2-arachidonoylglycerol (2-AG) also plays an important role on proper placentation and pregnancy success. However, THC impact on 2-AG homeostasis has never been addressed. Hence, the effects of THC in 2-AG levels and metabolic enzymes expression were explored. Long-term treatment impairs the expression of the main 2-AG synthetic and degradative enzymes. Curiously, with the highest concentration, despite the maintenance of diacylglycerol lipase alpha (DAGL alpha) and the decrease in monoacylglycerol lipase (MAGL) expression, 2-AG levels remain constant. Given the endocannabinoid signalling local tight regulation, we hypothesize the involvement of other 2-AG degradative enzymes. Indeed, THC increases the expression of the hydrolyzing enzymes alpha beta hydrolase domain-6 (ABHD6) and -12 (ABHD12), that we firstly describe in human placental tissues. The results show that THC, depending on time of exposure, induces alterations in 2-AG metabolic enzymes expression in placental explants, highlighting the importance of 2-AG regulation and endocannabinoid signalling in placental development. Alterations in this homeostasis may explain the negative pregnancy outcome related to cannabis consumption.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 7