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Low mRNA expression and activity of monoacylglycerol lipase in human SH-SY5Y neuroblastoma cells
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.ORCID iD: 0000-0001-8572-5841
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.ORCID iD: 0000-0002-6658-7874
2019 (English)In: Prostaglandins & other lipid mediators, ISSN 1098-8823, E-ISSN 2212-196X, Vol. 142, p. 59-67Article in journal (Refereed) Published
Abstract [en]

Relatively little is known about the endocannabinoid system in human neuroblastoma cell lines. In the present study, we have investigated the expression of the genes coding for the enzymes involved in the synthesis and catabolism of endocannabinoids in the SH-SY5Y cell line. The expression of MGLL, the gene coding for the 2-arachidonoylglycerol hydrolytic enzyme monoacylglycerol lipase (MAGL), was found to be 85 and 340 fold lower than the expression levels for the genes coding for alpha/beta-hydrolase domain containing 6 and 12 (ABHD6, ABHD12), which are alternative hydrolytic enzymes for this endocannabinoid. In comparison, mRNA levels of MGLL were 1.5 fold higher than ABHD6 and 2 fold lower than the levels of ABHD12 in DU-145 human prostate cells. In functional assays, the hydrolysis of the 2-arachidonoylglycerol homologue 2-oleoylglycerol by intact SH-SY5Y cells was partially inhibited by the ABHD6 inhibitor WWL70, but not by the MAGL inhibitor JZL184, whereas the reverse was true in DU-145 cells. The combination of JZL184 + WWL70 did, however produce a significantly greater inhibition of 2-OG hydrolysis than seen with WWL70 alone in the SH-SY5Y cells. The low MGLL expression in the SH-SY5Y cells was not due to epigenetic silencing, since levels were not affected by treatment with the methylation inhibitor 5-aza-2'-deoxycytidine and/or the histone acetylase inhibitor trichostatin A. The low MGLL expression in SH-SY5Y cells should be taken into account when using these cells in experiments investigating the involvement of the endocannabinoid system in models of physiological and pathological processes.

Place, publisher, year, edition, pages
Elsevier, 2019. Vol. 142, p. 59-67
Keywords [en]
Monoacylglycerol Llipase, SH-SY5Y cells, Neuroblastoma, Endocannabinoid, DU-145 cells
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-160287DOI: 10.1016/j.prostaglandins.2019.04.003ISI: 000469159100007PubMedID: 30978461OAI: oai:DiVA.org:umu-160287DiVA, id: diva2:1326059
Available from: 2019-06-17 Created: 2019-06-17 Last updated: 2019-06-17Bibliographically approved

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Karlsson, JessicaAlhouayek, MireilleFowler, Christopher J

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