title: Peroxide-Dependent MGL Sulfenylation Regulates 2-AG-Mediated Endocannabinoid Signaling in Brain Neurons.
abstract: The second messenger hydrogen peroxide transduces changes in the cellular redox state by reversibly oxidizing protein cysteine residues to sulfenic acid. This signaling event regulates many cellular processes but has never been shown to occur in the brain. Here, we report that hydrogen peroxide heightens endocannabinoid signaling in brain neurons through sulfenylation of cysteines C201 and C208 in monoacylglycerol lipase (MGL), a serine hydrolase that deactivates the endocannabinoid 2-arachidonoyl-sn-glycerol (2-AG) in nerve terminals. The results suggest that MGL sulfenylation may provide a presynaptic control point for 2-AG-mediated endocannabinoid signaling.
authors.affiliation: Department of Pharmacology, University of California, Irvine, Irvine, CA 92697, USA.
authors.forename: Emmanuel Y
authors.initials: EY
authors.lastname: Dotsey
authors.affiliation: Department of Anatomy and Neurobiology, University of California, 3101 Gillespie NRF, Irvine, CA 92697-1275, USA.
authors.forename: Kwang-Mook
authors.initials: KM
authors.lastname: Jung
authors.affiliation: Drug Discovery and Development, Istituto Italiano di Tecnologia, 16163 Genoa, Italy.
authors.forename: Abdul
authors.initials: A
authors.lastname: Basit
authors.affiliation: Department of Anatomy and Neurobiology, University of California, 3101 Gillespie NRF, Irvine, CA 92697-1275, USA.
authors.forename: Don
authors.initials: D
authors.lastname: Wei
authors.affiliation: Department of Anatomy and Neurobiology, University of California, 3101 Gillespie NRF, Irvine, CA 92697-1275, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Daglian
authors.affiliation: Dipartimento Farmaceutico, University of Parma, Parma 43100, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Vacondio
authors.affiliation: Drug Discovery and Development, Istituto Italiano di Tecnologia, 16163 Genoa, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Armirotti
authors.affiliation: Dipartimento Farmaceutico, University of Parma, Parma 43100, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Mor
authors.affiliation: Department of Pharmacology, University of California, Irvine, Irvine, CA 92697, USA; Department of Anatomy and Neurobiology, University of California, 3101 Gillespie NRF, Irvine, CA 92697-1275, USA; Drug Discovery and Development, Istituto Italiano di Tecnologia, 16163 Genoa, Italy; Department of Biological Chemistry, University of California, Irvine, Irvine, CA 92697, USA. Electronic address: piomelli@uci.edu.
authors.forename: Daniele
authors.initials: D
authors.lastname: Piomelli
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D002478:Cells, Cultured; D003545:Cysteine / Q000737:chemistry / Q000378:metabolism; D063388:Endocannabinoids / Q000378:metabolism*; D005260:Female; D005989:Glycerides / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008994:Monoacylglycerol Lipases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D015398:Signal Transduction; D013434:Sulfenic Acids / Q000737:chemistry*
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D043884:Receptor, Cannabinoid, CB1; D011994:Recombinant Proteins; D013434:Sulfenic Acids; C094503:glyceryl 2-arachidonate; D006861:Hydrogen Peroxide; D008994:Monoacylglycerol Lipases; D003545:Cysteine