Source:http://linkedlifedata.com/resource/pubmed/id/15272052
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2004-10-21
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pubmed:abstractText |
The endogenous cannabinoid 2-arachidonoylglycerol (2-AG) is produced by neurons and other cells in a stimulus-dependent manner and undergoes rapid biological inactivation through transport into cells and catalytic hydrolysis. The enzymatic pathways responsible for 2-AG degradation are only partially understood. We have shown previously that overexpression of monoacylglycerol lipase (MGL), a cytosolic serine hydrolase that cleaves 1- and 2-monoacylglycerols to fatty acid and glycerol, reduces stimulus-dependent 2-AG accumulation in primary cultures of rat brain neurons. We report here that RNA interference-mediated silencing of MGL expression greatly enhances 2-AG accumulation in HeLa cells. After stimulation with the calcium ionophore ionomycin, 2-AG levels in MGL-silenced cells were comparable with those found in cells in which 2-AG degradation had been blocked using methyl arachidonyl fluorophosphonate, a nonselective inhibitor of 2-AG hydrolysis. The results indicate that MGL plays an important role in the degradation of endogenous 2-AG in intact HeLa cells. Furthermore, immunodepletion experiments show that MGL accounts for at least 50% of the total 2-AG-hydrolyzing activity in soluble fractions of rat brain, suggesting that this enzyme also contributes to 2-AG deactivation in the central nervous system.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-arachidonylglycerol,
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Endocannabinoids,
http://linkedlifedata.com/resource/pubmed/chemical/Glycerides,
http://linkedlifedata.com/resource/pubmed/chemical/Monoacylglycerol Lipases,
http://linkedlifedata.com/resource/pubmed/chemical/Oligonucleotides
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0026-895X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
66
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1260-4
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:15272052-Animals,
pubmed-meshheading:15272052-Arachidonic Acids,
pubmed-meshheading:15272052-Brain,
pubmed-meshheading:15272052-Cells, Cultured,
pubmed-meshheading:15272052-Endocannabinoids,
pubmed-meshheading:15272052-Gene Silencing,
pubmed-meshheading:15272052-Glycerides,
pubmed-meshheading:15272052-HeLa Cells,
pubmed-meshheading:15272052-Humans,
pubmed-meshheading:15272052-Hydrolysis,
pubmed-meshheading:15272052-Monoacylglycerol Lipases,
pubmed-meshheading:15272052-Oligonucleotides,
pubmed-meshheading:15272052-RNA Interference,
pubmed-meshheading:15272052-Rats
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pubmed:year |
2004
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pubmed:articleTitle |
RNA interference suggests a primary role for monoacylglycerol lipase in the degradation of the endocannabinoid 2-arachidonoylglycerol.
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pubmed:affiliation |
Department of Pharmacology, University of California, Irvine, 360 Med Surge II, Irvine, CA 92697, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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