Acyl and phosphoryl migration in lysophospholipids: importance in phospholipid synthesis and phospholipase specificity

Plückthun, Andreas; Dennis, Edward A.

doi:10.1021/bi00537a007

Cited by 245 publications

(159 citation statements)

References 51 publications

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“…In accordance with this observation, in Chinese hamster ovary cells that have endogenous LPA receptors, p2y5-overexpression had no effect on the Ca 2ϩ signaling by LPA (12). Even in the presence of the promiscuous G protein, G 16 (44), p2y5-dependent Ca 2ϩ signaling was not observed in RH7777 cells (data not shown). (Fig.…”

Section: Discussionsupporting

confidence: 70%

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Identification and Characterization of a Novel Lysophosphatidic Acid Receptor, p2y5/LPA6

Yanagida

Masago²,

Nakanishi

et al. 2009

Journal of Biological Chemistry

240

207

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p2y5 is an orphan G protein-coupled receptor that is closely related to the fourth lysophosphatidic acid (LPA) receptor, LPA 4 . Here we report that p2y5 is a novel LPA receptor coupling to the G 13 -Rho signaling pathway. "LPA receptor-null" RH7777 and B103 cells exogenously expressing p2y5 showed [ 3 H]LPA binding, LPA-induced [35 S]guanosine 5-3-O-(thio)triphosphate binding, Rho-dependent alternation of cellular morphology, and G s/13 chimeric protein-mediated cAMP accumulation. LPA-induced contraction of human umbilical vein endothelial cells was suppressed by small interfering RNA knockdown of endogenously expressed p2y5. We also found that 2-acyl-LPA had higher activity to p2y5 than 1-acyl-LPA. A recent study has suggested that p2y5 is an LPA receptor essential for human hair growth. We confirmed that p2y5 is a functional LPA receptor and propose to designate this receptor LPA 6 .Lysophosphatidic acid (LPA 3 ; 1-or 2-acyl-sn-glycero-3-phosphate) is a naturally occurring lipid mediator with diverse biological activities (1, 2). LPA plays important roles in many biological processes, such as the nervous system (3), tumor metastasis (4), wound healing (5), cardiovascular functions (6), and reproduction (7), through its specific G protein-coupled receptors (GPCRs). At least five subtypes of LPA receptors have been identified. Three receptors (LPA 1 (8), LPA 2 (9), and LPA 3 (10, 11)) share about 50% amino acid sequence identities, and form the Edg (endothelial differentiation gene) family together with the GPCRs for sphingosine 1-phosphate. Two additional LPA receptors, p2y9/LPA 4 (12) and GPR92/LPA 5 (13, 14), which show small similarities with the Edg family GPCRs, were recently identified. These LPA receptors, by coupling with different sets of G proteins, transduce various responses in many cell types. Depending on the functional coupling of a given LPA receptor to the G proteins, LPA activates diverse signaling cascades involving phosphoinositide 3-kinase, phospholipase C, mitogen-activated protein kinase, Rho-family GTPase, and adenylyl cyclase (2).The fact that p2y5 shares the highest sequence homology with p2y9/LPA 4 among all GPCRs (12) strongly suggested that LPA is a ligand for p2y5. However, we could not detect LPAinduced Ca 2ϩ mobilization or cAMP level changes in p2y5-overexpressing cells at the time of the identification of p2y9/ LPA 4 as the fourth LPA receptor in our laboratory (12). In the course of the further analysis of p2y5-overexpressing cells, we found that p2y5 actually responded to LPA with activation of the G 13 -Rho signaling pathway. Our results confirm the identification of p2y5 as an LPA receptor and extend the knowledge of the functional roles of LPA. EXPERIMENTAL PROCEDURESLipids-1-Oleoyl-LPA, 1-palmitoyl-LPA, 1-stearoyl-LPA, 1-myristoyl-LPA, and 1-arachidonoyl-LPA were purchased from Avanti Polar Lipids (Alabaster, AL). 1-Linoleoyl-LPA was from Echelon Biosciences (Salt Lake City, UT). These lipids were stored at Ϫ30°C (10 mM stock in 50% ethanol). Alkyl-OMPT (10 mM stock in d...

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Section: Discussionsupporting

confidence: 70%

“…2-Acyl-LPA was eluted with methanol after the washing with water. Since 2-acyl-LPA is unstable (16), we used the fraction within 2 h after the elution. The amount of LPA in the eluted fraction was determined by phosphoric analysis after the separation of LPA by thin layer chromatography.…”

Section: Methodsmentioning

confidence: 99%

Identification and Characterization of a Novel Lysophosphatidic Acid Receptor, p2y5/LPA6

Yanagida

Masago²,

Nakanishi

et al. 2009

Journal of Biological Chemistry

240

207

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“…14 C]Palmitoylglycero-3-phosphocholine and L-␣- 2-Palmitoylglycero-3-phosphocholine (2-PGPC) was prepared by treating 1,2-dipalmitoyl-sn-glycero-3-phosphocholine with Rhizopus lipase following published procedures (20). Conversion of 1,2-dipalmitoylsn-glycero-3-phosphocholine to 2-PGPC did not proceed to completion.…”

Section: Materials-l-␣-1-[mentioning

confidence: 99%

“…Similarly, commercial 1-PGPC contains ϳ10% of the corresponding 2-PGPC isomer. These cross-contaminations have been documented and are attributed to migration of the fatty acyl chain during the preparation and purification of lysophospholipids (20). Appropriate amounts of 1-PGPC and 2-PGPC were combined to give a 1:1 mixture of isomers.…”

Section: Materials-l-␣-1-[mentioning

confidence: 99%

Activation, Inhibition, and Regiospecificity of the Lysophospholipase Activity of the 85-kDa Group IV Cytosolic Phospholipase A2

Loo

Conde‐Frieboes

Reynolds

et al. 1997

Journal of Biological Chemistry

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The 85-kDa Group IV calcium-dependent cytosolic phospholipase A 2 (cPLA 2 ) catalyzes the hydrolysis of palmitoylglycero-3-phosphocholine to palmitic acid and glycero-3-phosphocholine. Palmitoylglycero-3-phosphocholine exists as a 9:1 equilibrium mixture of the sn-1 and sn-2 isomers, with the fatty acid predominately at the sn-1 position. We have monitored this reaction by 31 P NMR to determine which palmitoylglycero-3-phosphocholine isomer is processed by cPLA 2 . When both lysophospholipid isomers are present in a 1:1 mixture under conditions in which acyl migration is minimized, cPLA 2 rapidly consumes both isomers. However, 1-palmitoylglycero-3-phosphocholine is consumed seven times faster than the 2-palmitoylglycero-3-phosphocholine isomer. We have previously reported that this lysophospholipase reaction is accelerated in the presence of glycerol. We now find that this apparent increase in activity is accounted for, in part, by glycerol acting as an alternative acceptor for the cleaved fatty acid, as is the case for this enzyme's phospholipase A 2 (PLA 2 ) activity. In contrast, dioleoylglycerol, which accelerates the PLA 2 activity, does not act as an acceptor in either the lysophospholipase or the PLA 2 reaction, but can affect enzyme activities by altering substrate presentation. We also show that a known inhibitor of the PLA 2 activity of cPLA 2 is able to inhibit its lysophospholipase activity with a similar IC 50 to its PLA 2 activity. However, the effect of inhibitors is dependent on the manner in which they are presented to the enzyme.

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“…5D, E). One should note that a partial migration of the fatty acid residue from the sn-2 to the sn-1 position takes place in mixed detergent-phospholipid micelles (35). Thus, a second resonance of the correspond-…”

mentioning

confidence: 98%

Hypochlorous acid-mediated generation of glycerophosphocholine from unsaturated plasmalogen glycerophosphocholine lipids

Lessig

Schiller

Arnhold

et al. 2007

Journal of Lipid Research

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The myeloperoxidase-derived metabolite hypochlorous acid (HOCl) promotes the selective cleavage of plasmalogens into chloro fatty aldehydes and 1-lysophosphatidylcholine (LPC). The subsequent conversion of the initially generated LPC was investigated in plasmalogen samples in dependence on the fatty acid residue in the sn-2 position by matrix-assisted laser desorption and ionization time-of-flight mass spectrometry and 31 P NMR spectroscopy. Plasmalogens containing an oleic acid residue in the sn-2 position are converted by moderate amounts of HOCl primarily to 1-lyso-2-oleoyl-sn-glycero-3-phosphocholine and at increased HOCl concentrations to the corresponding chlorohydrin species. In contrast, plasmalogens containing highly unsaturated docosahexaenoic acid yield upon HOCl treatment 1-lyso-2-docosahexaenoyl-glycerophosphocholine and glycerophosphocholine. The formation of the latter product denotes a novel pathway for the action of HOCl on plasmalogens. Olefinic residues of fatty acyl residues of phospholipids are an important target for oxidative damage induced by reactive oxygen species (ROS) known to occur under various pathological conditions, including chronic inflammation, atherosclerosis, aging, and cancer. Some mammalian tissues and cells, such as erythrocytes, kidney, lung, testes, skeletal muscle, brain, heart, and particularly selected animal spermatozoa (e.g., from bull), contain considerable levels of plasmalogen glycerophosphocholine lipids (1). Plasmalogens also represent an important target for ROS (2) and are often considered antioxidants. Although the 1-alkenyl residues in plasmalogens (mainly plasmalogen glycerophosphocholine and glycerophosphoethanolamine) of mammalian cells are usually derived from saturated long-chain fatty aldehydes, the acyl residues are highly unsaturated (2). For instance, in spermatozoa from boar or bull, docosahexaenoic and docosapentaenoic acid residues do nearly occur exclusively (3). Accordingly, the oxidative attack of ROS may affect the vinyl-ether function as well as the olefinic residue in the fatty acid moiety (4). The presence of a vinyl-ether bond makes plasmalogens more susceptible to oxidative damages compared with their 1-acyl analogs (2). This has prompted the hypothesis that plasmalogens may act as ROS scavengers, protecting other phospholipids and lipoprotein particles from oxidative damage (2). Thus, plasmalogens seem to have an antioxidative effect toward many ROS (5).Hypochlorous acid (HOCl) is generated by polymorphonuclear leukocytes under the catalysis of the enzyme myeloperoxidase (MPO) (6). HOCl reacts with a variety of molecules, including amino acids, proteins, carbohydrates, nucleic acids, and lipids (7-12). In the latter case, chlorohydrins are generated as the primary products when HOCl reacts with the double bonds in unsaturated phosphatidylcholines (12)(13)(14). HOCl and the MPO-H 2 O 2 -Cl 2 system also induce the formation of 2-lysophosphatidylcholines (LPCs) in polyunsaturated phosphatidylcholines, as shown by matrixassisted...

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Acyl and phosphoryl migration in lysophospholipids: importance in phospholipid synthesis and phospholipase specificity

Cited by 245 publications

References 51 publications

Identification and Characterization of a Novel Lysophosphatidic Acid Receptor, p2y5/LPA6

Identification and Characterization of a Novel Lysophosphatidic Acid Receptor, p2y5/LPA6

Activation, Inhibition, and Regiospecificity of the Lysophospholipase Activity of the 85-kDa Group IV Cytosolic Phospholipase A2

Hypochlorous acid-mediated generation of glycerophosphocholine from unsaturated plasmalogen glycerophosphocholine lipids

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