N-Acylethanolamines and precursor phospholipids — relation to cell injury

Hansen, Harald S.; Moesgaard, Birthe; Hansen, Henrik H.; Petersen, Gitte

doi:10.1016/s0009-3084(00)00192-4

Cited by 206 publications

(158 citation statements)

References 125 publications

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“…NAPEs not only serve as precursors to NAEs, but also have biological functions of their own. Increasing NAPE levels together with their product NAEs after neuronal damage 5, 6, 7 are indicative of their involvement in a neuroprotective mechanism 8, 9. Postprandial increase of NAPE levels and inhibition of food intake by their administration, may suggest a potential anorectic role 10, 11, although this is subject of controversy and has not yet been clearly shown 1.…”

Section: Introductionmentioning

confidence: 99%

Quantitative analysis of N‐acylphosphatidylethanolamine molecular species in rat brain using solid‐phase extraction combined with reversed‐phase chromatography and tandem mass spectrometry

Triebl

Weissengruber

Trötzmüller

et al. 2016

J of Separation Science

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A novel method for the sensitive and selective identification and quantification of N‐acylphosphatidylethanolamine molecular species was developed. Samples were prepared using a combination of liquid–liquid and solid‐phase extraction, and intact N‐acylphosphatidylethanolamine species were determined by reversed‐phase high‐performance liquid chromatography coupled to positive electrospray tandem mass spectrometry. As a result of their biological functions as precursors for N‐acylethanolamines and as signaling molecules, tissue concentrations of N‐acylphosphatidylethanolamines are very low, and their analysis is additionally hindered by the vast excess of other sample components. Our sample preparation methods are able to selectively separate the analytes of interest from any expected biological interferences. Finally, the highest selectivity is achieved by coupling chromatographic separation and two N‐acyl chain specific selected reaction monitoring scans per analyte, enabling identification of both the N‐acyl chain and the phosphatidylethanolamine moiety. The validated method is suitable for the reliable quantification of N‐acylphosphatidylethanolamine species from rat brain with a lower limit of quantification of 10 pmol/g and a linear range up to 2300 pmol/g. In total, 41 N‐acylphosphatidylethanolamine molecular species with six different N‐acyl chains, amounting to a total concentration of 3 nmol/g, were quantified.

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Section: Introductionmentioning

confidence: 99%

Quantitative analysis of N‐acylphosphatidylethanolamine molecular species in rat brain using solid‐phase extraction combined with reversed‐phase chromatography and tandem mass spectrometry

Triebl

Weissengruber

Trötzmüller

et al. 2016

J of Separation Science

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“…because of their presence in a variety of organisms and their biological activities (1,2). For example, anandamide (N-arachidonoylethanolamine) acts as a ligand of cannabinoid receptors (3) and the vanilloid receptor (4) in mammalian tissues.…”

mentioning

confidence: 99%

Discovery and Characterization of a Ca2+-independent Phosphatidylethanolamine N-Acyltransferase Generating the Anandamide Precursor and Its Congeners

Jin

Okamoto

Morishita

et al. 2007

Journal of Biological Chemistry

133

105

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N-Acylphosphatidylethanolamines (NAPEs) are precursors of bioactive N-acylethanolamines, including the endocannabinoid anandamide. In animal tissues, NAPE is formed by transfer of a fatty acyl chain at the sn-1 position of glycerophospholipids to the amino group of phosphatidylethanolamine (PE), and this reaction is believed to be the principal rate-limiting step in N-acylethanolamine synthesis. However, the Ca 2؉ -dependent, membrane-associated N-acyltransferase (NAT) responsible for this reaction has not yet been cloned. In this study, on the basis of the functional similarity of NAT to lecithin-retinol acyltransferase (LRAT), we examined a possible PE N-acylation activity in two rat LRAT homologous proteins. Upon overexpression in COS-7 cells, one protein, named rat LRAT-like protein (RLP)-1, catalyzed transfer of a radioactive acyl group from phosphatidylcholine (PC) to PE, resulting in the formation of radioactive NAPE. However, the RLP-1 activity was detected mainly in the cytosolic rather than membrane fraction and was little stimulated by Ca 2؉ . Moreover, RLP-1 did not show selectivity with respect to the sn-1 and sn-2 positions of PC as an acyl donor and therefore could generate N-arachidonoyl-PE (anandamide precursor) from 2-arachidonoyl-PC and PE. In contrast, under the same assay conditions, partially purified NAT from rat brain was highly Ca 2؉ -dependent, membrane-associated, and specific for the sn-1-acyl group of PC. RLP-1 mRNA was expressed predominantly in testis among various rat tissues, and the testis cytosol exhibited an RLP-1-like activity. These results reveal that RLP-1 can function as a PE N-acyltransferase, catalytically distinguishable from the known Ca 2؉ -dependent NAT.

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“…In animal systems, anandamide (NAE 20:4) acts as an endogenous ligand for cannabinoid receptors and has varied physiological roles, such as the modulation of neurotransmission in the central nervous system (2). Anandamide also activates vanilloid receptors, functions as an endogenous analgesic (3), and appears to be involved in neuroprotection (4,5). In other tissues, NAEs have been implicated in immunomodulation (6), synchronization of embryo development (7), and induction of apoptosis (8).…”

mentioning

confidence: 99%

Molecular Identification of a Functional Homologue of the Mammalian Fatty Acid Amide Hydrolase in Arabidopsis thaliana

Shrestha

Dixon

Chapman

2003

Journal of Biological Chemistry

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N-Acylethanolamines (NAEs) are endogenous constituents of plant and animal tissues, and in vertebrates their hydrolysis terminates their participation as lipid mediators in the endocannabinoid signaling system. The membrane-bound enzyme responsible for NAE hydrolysis in mammals has been identified at the molecular level (designated fatty acid amide hydrolase, FAAH), and although an analogous enzyme activity was identified in microsomes of cotton seedlings, no molecular information is available for this enzyme in plants. Here we report the identification, the heterologous expression (in Escherichia coli), and the biochemical characterization of an Arabidopsis thaliana FAAH homologue. Candidate Arabidopsis DNA sequences containing a characteristic amidase signature sequence (PS00571) were identified in plant genome data bases, and a cDNA was isolated by reverse transcriptase-PCR using Arabidopsis genome sequences to develop appropriate oligonucleotide primers. The cDNA was sequenced and predicted to encode a protein of 607 amino acids with 37% identity to rat FAAH within the amidase signature domain (18% over the entire length). Residues determined to be important for FAAH catalysis were conserved between the Arabidopsis and rat protein sequences. In addition, a single transmembrane domain near the N terminus was predicted in the Arabidopsis protein sequence, similar to that of the rat FAAH protein. The putative plant FAAH cDNA was expressed as an epitope/ His-tagged fusion protein in E. coli and solubilized from cell lysates in the nonionic detergent, dodecyl maltoside. Affinity-purified recombinant protein was indeed active in hydrolyzing a variety of naturally occurring N-acylethanolamine types. Kinetic parameters and inhibition data for the recombinant Arabidopsis protein were consistent with these properties of the enzyme activity characterized previously in plant and animal systems. Collectively these data now provide support at the molecular level for a conserved mechanism between plants and animals for the metabolism of NAEs.N-Acylethanolamines (NAEs) 1 are lipid mediators that are produced from the phospholipase D-mediated hydrolysis of Nacylphosphatidylethanolamines, a minor membrane lipid constituent of cellular membranes (1). In animal systems, anandamide (NAE 20:4) acts as an endogenous ligand for cannabinoid receptors and has varied physiological roles, such as the modulation of neurotransmission in the central nervous system (2). Anandamide also activates vanilloid receptors, functions as an endogenous analgesic (3), and appears to be involved in neuroprotection (4,5). In other tissues, NAEs have been implicated in immunomodulation (6), synchronization of embryo development (7), and induction of apoptosis (8). These endogenous bioactive molecules lose their signaling activity upon hydrolysis by fatty acid amide hydrolase (FAAH; see Ref. 9).In plants NAEs are present in substantial amounts in desiccated seeds (ϳ1 g g Ϫ1 fresh weight), and their levels decline after a few hours of imbibition (10). Ind...

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N-Acylethanolamines and precursor phospholipids — relation to cell injury

Cited by 206 publications

References 125 publications

Quantitative analysis of N‐acylphosphatidylethanolamine molecular species in rat brain using solid‐phase extraction combined with reversed‐phase chromatography and tandem mass spectrometry

Quantitative analysis of N‐acylphosphatidylethanolamine molecular species in rat brain using solid‐phase extraction combined with reversed‐phase chromatography and tandem mass spectrometry

Discovery and Characterization of a Ca2+-independent Phosphatidylethanolamine N-Acyltransferase Generating the Anandamide Precursor and Its Congeners

Molecular Identification of a Functional Homologue of the Mammalian Fatty Acid Amide Hydrolase in Arabidopsis thaliana

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