Cloning and Characterization of Mouse Lung-type Acyl-CoA:Lysophosphatidylcholine Acyltransferase 1 (LPCAT1)

Nakanishi, Hiroki; Shindou, Hideo; Hishikawa, Daisuke; Harayama, Takeshi; Ogasawara, Rie; Suwabe, Akira; Taguchi, Ryo; Shimizu, Takao

doi:10.1074/jbc.m600225200

Cited by 220 publications

(238 citation statements)

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“…The rapid turnover of the sn-2 acyl chains of glycerophospholipids was originally described by Lands (Lands, 1958;Lands, 1960;Lands and Merkl, 1963;Merkl and Lands, 1963), who proposed that acyl moieties of membrane phospholipids are rapidly metabolized by the action of phospholipase A 2 s and subsequently by lysophospholipid acyltransferases (Lands' cycle). To date, at least two lysophosphatidylcholine acyltransferases (LPCAT) were cloned from mammals: LPCAT1) catalyzes the incorporation of saturated fatty acids into lysoThis article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E07-09 -0893) on December 19, 2007. phosphatidylcholine (lysoPC) (Chen et al, 2006;Nakanishi et al, 2006), and LPCAT2 catalyzes the incorporation of acetic acid and AA into lysoPC (Shindou et al, 2007). These enzymes have conserved motifs in common with the enzymes involved in the de novo phospholipid synthesis pathway (Kennedy pathway) such as acylglycerolphosphate acyltransferase and lysophosphatidic acid acyltransferase (LPAAT).…”

Section: Introductionmentioning

confidence: 99%

“…© 2008 by The American Society for Cell Biology phosphatidylcholine (lysoPC) (Chen et al, 2006;Nakanishi et al, 2006), and LPCAT2 catalyzes the incorporation of acetic acid and AA into lysoPC (Shindou et al, 2007). These enzymes have conserved motifs in common with the enzymes involved in the de novo phospholipid synthesis pathway (Kennedy pathway) such as acylglycerolphosphate acyltransferase and lysophosphatidic acid acyltransferase (LPAAT).…”

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Caenorhabditis elegans mboa-7, a Member of the MBOAT Family, Is Required for Selective Incorporation of Polyunsaturated Fatty Acids into Phosphatidylinositol

Lee

Inoué

Imae

et al. 2008

MBoC

125

117

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Phosphatidylinositol (PI) is a component of membrane phospholipids, and it functions both as a signaling molecule and as a compartment-specific localization signal in the form of polyphosphoinositides. Arachidonic acid (AA) is the predominant fatty acid in the sn-2 position of PI in mammals. LysoPI acyltransferase (LPIAT) is thought to catalyze formation of AA-containing PI; however, the gene that encodes this enzyme has not yet been identified. In this study, we established a screening system to identify genes required for use of exogenous polyunsaturated fatty acids (PUFAs) in Caenorhabditis elegans. In C. elegans, eicosapentaenoic acid (EPA) instead of AA is the predominant fatty acid in PI. We showed that an uncharacterized gene, which we named mboa-7, is required for incorporation of PUFAs into PI. Incorporation of exogenous PUFA into PI of the living worms and LPIAT activity in the microsomes were greatly reduced in mboa-7 mutants. Furthermore, the membrane fractions of transgenic worms expressing recombinant MBOA-7 and its human homologue exhibited remarkably increased LPIAT activity. mboa-7 encodes a member of the membrane-bound O-acyltransferase family, suggesting that mboa-7 is LPIAT. Finally, mboa-7 mutants had significantly lower EPA levels in PI, and they exhibited larval arrest and egg-laying defects. INTRODUCTIONVarious kinds of fatty acids are distributed in membrane phospholipids in mammalian cells and tissues (Lands and Crawford, 1976;Holub and Kuksis, 1978;MacDonald and Sprecher, 1991). The fatty acyl residues of individual phospholipids seem to be under strict metabolic regulation. In general, saturated fatty acids are esterified at the sn-1 position, whereas polyunsaturated fatty acids (PUFAs), such as arachidonic acid (AA), are commonly found at the sn-2 position. Three-fourths or more of the phosphatidylinositol (PI) fraction in rat liver and brain constitutes the 1-stearoyl-2-arachidonoyl species (Holub and Kuksis, 1971;Baker and Thompson, 1972). In contrast, the total pool of precursor phosphatidic acid (PA) in rat liver and brain has a fatty acid composition that does not resemble that of PI, showing a low AA content (Possmayer et al., 1969;Akesson et al., 1970;Baker and Thompson, 1972). Selectivity could be expressed during de novo synthesis at the level of formation of cytidine 5Ј-diphosphate (CDP)-diacylglycerol from PA and cytidine 5Ј-triphosphate or in the use of CDP-diacylglycerol in the final reaction. In fact, CDP-diacylglycerol synthase, which prefers 1-stearoyl-2-arachidonoyl PA as a substrate in vitro, has been cloned, although expression is restricted to testis, retina, and brain (Saito et al., 1997).An alternative mechanism for species selection has been proposed on the basis of turnover studies in rat brain in vivo (Baker and Thompson, 1972). [ 3 H]AA and [ 14 C]glycerol injected intracerebrally were incorporated almost exclusively into brain phospholipids. Comparison of PI and PA radioactivity suggest that the initial flux of AA into PI was independent of de novo synthesi...

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Section: Introductionmentioning

confidence: 99%

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confidence: 99%

Caenorhabditis elegans mboa-7, a Member of the MBOAT Family, Is Required for Selective Incorporation of Polyunsaturated Fatty Acids into Phosphatidylinositol

Lee

Inoué

Imae

et al. 2008

MBoC

125

117

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“…Since PC synthesis occurs in a variety of different tissues, additional LPC acyltransferases may be present for membrane biogenesis. Using the previously reported LPCAT1 (27) and an extensive genomic data base search as well as 5Ј-and 3Ј-RACE, we have identified a lyso-PAF acetyltransferase gene. The enzyme is primarily expressed in inflammatory cells and is induced by LPS.…”

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confidence: 99%

“…Rapid turnover of the sn-2 acyl moiety of glycerophospholipids was described by Lands (Lands' cycle) (24 -26) and is attributed to activation of phospholipases A 2 and lysophospholipid acyltransferases. Recently, we (27) and Chen et al (28) independently cloned one of LPC acyltrans-* This work was supported in part by Grants-in-Aid from the Ministry of Education, Science, Culture, Sports, and Technology of Japan (to T. S. and S. I.).…”

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confidence: 99%

“…To our knowledge, this is the first documentation of a cDNA for LysoPAFAT/LPCAT2, a critically important enzyme in the biogenesis of PAF and in membrane homeostasis of inflammatory cells. Cloning of LysoPAFAT/LPCAT2-The mLysoPAFAT/ LPCAT2 gene was identified based upon sequence similarity to the LPCAT1 gene (27) and LPA acyltransferase gene (29) through a comprehensive basic local alignment search tool (BLAST) search. A 1.6-kb cDNA clone encoding the full-length mLysoPAFAT/LPCAT2 (DDBJ accession number AB244716) was cloned by PCR amplification using the forward primer 5Ј-CTAGCTAGCCACCATGGATTACAAGGATGACGAT-GACAAGAACCGATGCGCCGAGGCGGCCGC-3Ј, the reverse primer 5Ј-CCGCTCGAGTCAGTCCACCTTTTTGTC-TGAGGTGCCCTC-3Ј, and a mouse spleen cDNA library as a template.…”

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A Single Enzyme Catalyzes Both Platelet-activating Factor Production and Membrane Biogenesis of Inflammatory Cells

Shindou¹,

Hishikawa²,

Nakanishi

et al. 2007

Journal of Biological Chemistry

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223

239

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Platelet-activating factor (PAF) is a potent proinflammatory lipid mediator eliciting a variety of cellular functions. Lipid mediators, including PAF are produced from membrane phospholipids by enzymatic cascades. Although a G protein-coupled PAF receptor and degradation enzymes have been cloned and characterized, the PAF biosynthetic enzyme, aceyl-CoA:lyso-PAF acetyltransferase, has not been identified. Here, we cloned lyso-PAF acetyltransferase, which is critical in stimulusdependent formation of PAF. The enzyme is a 60-kDa microsomal protein with three putative membrane-spanning domains. The enzyme was induced by bacterial endotoxin (lipopolysaccharide), which was suppressed by dexamethasone treatment. Surprisingly, the enzyme catalyzed not only biosynthesis of PAF from lyso-PAF but also incorporation of arachidonoyl-CoA to produce PAF precursor membrane glycerophospholipids (lysophosphatidylcholine acyltransferase activity). Under resting conditions, the enzyme prefers arachidonoyl-CoA and contributes to membrane biogenesis. Upon acute inflammatory stimulation with lipopolysaccharide, the activated enzyme utilizes acetyl-CoA more efficiently and produces PAF. Thus, our findings provide a novel concept that a single enzyme catalyzes membrane biogenesis of inflammatory cells while producing a prophlogistic mediator in response to external stimuli.Platelet-activating factor (PAF 3 ; 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a phospholipid mediator that activates a G protein-coupled receptor (1-3) and results in pleiotropic and potent biological effects, including platelet activation, airway constriction, and hypotension (1). PAF is synthesized in various cells and tissues via two distinct pathways, the de novo and remodeling pathways (2, 4, 5), and the latter is regulated by extracellular signals and plays a critical role in stimulus-coupled PAF biosynthesis (2, 4 -6). PAF synthesis induced by extracellular signals has been reported in murine peritoneal cells stimulated by calcium ionophore (7) or by PAF (8), in human eosinophils stimulated by fMet-Leu-Phe (9), in human neutrophils stimulated by acid stress (10), and in murine peritoneal macrophages stimulated by lipopolysaccharide (LPS) (11). In the remodeling pathway, the precursor of PAF, 1-Oalkyl-sn-glycero-3-phosphocholine (lyso-PAF), is synthesized from 1-O-alkyl-2-arachidonoyl-sn-glycero-3-phosphocholine (1-alkyl-phosphatidylcholine; PC) by the action of phospholipase A 2 (2, 4, 12, 13). Subsequently, lyso-PAF is converted to PAF by acetyl-CoA:lyso-PAF acetyltransferase (lyso-PAF acetyltransferase) (EC 2.3.1.67) (14). PAF is then rapidly degraded to lyso-PAF by PAF acetylhydrolases (15). Alternatively, lyso-PAF is again transformed into PC by the action of lysophosphatidylcholine (LPC) acyltransferase (2.3.1.23) (16).A G protein-coupled PAF receptor was cloned in our laboratory (17), and PAF acetylhydrolases have been cloned and characterized by others (18,19). Lyso-PAF acetyltransferase was initially demonstrated and partially characterized by ...

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MALDIMass Spectrometry Imaging of Biological Structures

Zaima

Goto‐Inoue

Hayasaka

2015

Encyclopedia of Analytical Chemistry

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Matrix‐assisted laser desorption/ionization (MALDI) is a ‘soft’ ionization method which enables the detection of several molecules including proteins, peptides, amino acids, sugars, lipids, and metabolites, in biological samples. The versatility of MALDI makes it essential analytical method to detect the molecules of interest in the complex biological structures. To take this advantage of MALDI, matrix‐assisted laser desorption/ionization mass spectrometry imaging (MALDI‐MSI) has been developed as a molecular imaging method to visualize the spatial distribution of molecules in biological sample section. It has been reported that almost all kinds of molecules, such as biomolecules and administrated drugs or food factors, in biological samples can be visualized by MALDI‐MSI. Because many of these molecules cannot be visualized with the exception of MALDI‐MSI, MALDI‐MSI opens a new frontier in several fields such as medical science, pharmaceutical science, plant science, and food science. To obtain biologically meaningful information of the distribution of molecules of interest, researcher should understand the basic experimental steps and potential applications of MALDI‐MSI. In this article, principle, basic experimental procedure, and applications of MALDI‐MSI are described.

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Cloning and Characterization of Mouse Lung-type Acyl-CoA:Lysophosphatidylcholine Acyltransferase 1 (LPCAT1)

Cited by 220 publications

References 52 publications

Caenorhabditis elegans mboa-7, a Member of the MBOAT Family, Is Required for Selective Incorporation of Polyunsaturated Fatty Acids into Phosphatidylinositol

Caenorhabditis elegans mboa-7, a Member of the MBOAT Family, Is Required for Selective Incorporation of Polyunsaturated Fatty Acids into Phosphatidylinositol

A Single Enzyme Catalyzes Both Platelet-activating Factor Production and Membrane Biogenesis of Inflammatory Cells

MALDIMass Spectrometry Imaging of Biological Structures

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