Document Detail


Leptin activates the anandamide hydrolase promoter in human T lymphocytes through STAT3.
MedLine Citation:
PMID:  12556536     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Physiological concentrations of leptin stimulate the activity of the endocannabinoid-degrading enzyme anandamide hydrolase (fatty acid amide hydrolase, FAAH) in human T lymphocytes up to approximately 300% over the untreated controls. Stimulation of FAAH occurred through up-regulation of gene expression at transcriptional and translational levels and involved binding of leptin to its receptor with an apparent dissociation constant (K(d)) of 1.95 +/- 0.14 nm and maximum binding (B(max)) of 392 +/- 8 fmol x mg protein(-1). Leptin binding to the receptor triggered activation of STAT3 but not STAT1 or STAT5 or the mitogen-activated protein kinases p38, p42, and p44. Peripheral lymphocytes of leptin knock-out (ob/ob) mice showed decreased FAAH activity and expression (approximately 25% of the wild-type littermates), which were reversed to control levels by exogenous leptin. Analysis of the FAAH promoter showed a cAMP-response element-like site, which is a transcriptional target of STAT3. Consistently, mutation of this site prevented FAAH activation by leptin in transient expression assays. Electrophoretic mobility shift and supershift assays further corroborated the promoter activity data. Taken together, these results suggest that leptin, by up-regulating the FAAH promoter through STAT3, enhances FAAH expression, thus tuning the immunomodulatory effects of anandamide. These findings might also have critical implications for human fertility.
Authors:
Mauro Maccarrone; Marianna Di Rienzo; Alessandro Finazzi-Agrò; Antonello Rossi
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-01-28
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  278     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2003 Apr 
Date Detail:
Created Date:  2003-04-07     Completed Date:  2003-07-03     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  13318-24     Citation Subset:  IM    
Affiliation:
Department of Biomedical Sciences, University of Teramo, Piazza A. Moro 45, 64100 Teramo, Italy. Maccarrone@vet.unite.it
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MeSH Terms
Descriptor/Qualifier:
Acute-Phase Proteins / metabolism
Amidohydrolases / genetics*
Base Sequence
DNA Primers
DNA-Binding Proteins / metabolism*
Endocannabinoids
Gene Expression Regulation, Enzymologic / drug effects*
Humans
Kinetics
Leptin / pharmacology*
Molecular Sequence Data
Polymerase Chain Reaction
Promoter Regions, Genetic*
Protein Biosynthesis
Receptors, Cell Surface / physiology
Receptors, Leptin
STAT3 Transcription Factor
T-Lymphocytes / enzymology,  physiology*
Trans-Activators / metabolism*
Transcription, Genetic
Chemical
Reg. No./Substance:
0/Acute-Phase Proteins; 0/DNA Primers; 0/DNA-Binding Proteins; 0/Endocannabinoids; 0/Leptin; 0/Receptors, Cell Surface; 0/Receptors, Leptin; 0/STAT3 Transcription Factor; 0/STAT3 protein, human; 0/Trans-Activators; 0/leptin receptor, human; EC 3.5.-/Amidohydrolases; EC 3.5.1.-/fatty-acid amide hydrolase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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