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.
Copyright © 2015 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Arachidonic Acids / metabolism*
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Brain / metabolism
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Cells, Cultured
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Cysteine / chemistry
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Cysteine / metabolism
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Endocannabinoids / metabolism*
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Female
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Glycerides / metabolism*
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HeLa Cells
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Humans
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Hydrogen Peroxide / chemistry
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Hydrogen Peroxide / metabolism
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Kinetics
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Monoacylglycerol Lipases / chemistry*
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Monoacylglycerol Lipases / genetics
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Monoacylglycerol Lipases / metabolism
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Mutagenesis, Site-Directed
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Neurons / cytology
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Neurons / metabolism*
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Protein Structure, Tertiary
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Rats
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Rats, Wistar
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Receptor, Cannabinoid, CB1 / metabolism
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / chemistry
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Recombinant Proteins / isolation & purification
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Signal Transduction
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Sulfenic Acids / chemistry*
Substances
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Arachidonic Acids
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Endocannabinoids
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Glycerides
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Receptor, Cannabinoid, CB1
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Recombinant Proteins
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Sulfenic Acids
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glyceryl 2-arachidonate
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Hydrogen Peroxide
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Monoacylglycerol Lipases
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Cysteine