title: Impact of embedded endocannabinoids and their oxygenation by lipoxygenase on membrane properties.
abstract: N-Arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol are the best characterized endocannabinoids. Their biological activity is subjected to metabolic control whereby a dynamic equilibrium among biosynthetic, catabolic, and oxidative pathways drives their intracellular concentrations. In particular, lipoxygenases can generate hydroperoxy derivatives of endocannabinoids, endowed with distinct activities within cells. The in vivo interaction between lipoxygenases and endocannabinoids is likely to occur within cell membranes; thus, we sought to ascertain whether a prototypical enzyme like soybean (Glycine max) 15-lipoxygenase-1 is able to oxygenate endocannabinoids embedded in synthetic vesicles and how these substances could affect the binding ability of the enzyme to different lipid bilayers. We show that (i) embedded endocannabinoids increase membrane fluidity; (ii) 15-lipoxygenase-1 preferentially binds to endocannabinoid-containing bilayers; and that (iii) 15-lipoxygenase-1 oxidizes embedded endocannabinoids and thus reduces fluidity and local hydration of membrane lipids. Together, the present findings reveal further complexity in the regulation of endocannabinoid signaling within the central nervous system, disclosing novel control by oxidative pathways.
authors.affiliation: Department of Biomedical Sciences, University of Teramo, Teramo, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Dainese
authors.forename: Annalaura
authors.initials: A
authors.lastname: Sabatucci
authors.forename: Clotilde B
authors.initials: CB
authors.lastname: Angelucci
authors.forename: Daniela
authors.initials: D
authors.lastname: Barsacchi
authors.forename: Marco
authors.initials: M
authors.lastname: Chiarini
authors.forename: Mauro
authors.initials: M
authors.lastname: Maccarrone
mesh_terms: D063388:Endocannabinoids / Q000737:chemistry / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008084:Lipoxygenase / Q000737:chemistry / Q000378:metabolism*; D008567:Membranes, Artificial; D010100:Oxygen / Q000378:metabolism*; D013025:Glycine max
chemical_list: D063388:Endocannabinoids; D008051:Lipid Bilayers; D008567:Membranes, Artificial; D008084:Lipoxygenase; D010100:Oxygen