関: lysophosphatidic acid

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/02 02:16:25」(JST)

wiki en

The lysophospholipid receptor (LPL-R) group are members of the G protein-coupled receptor family of integral membrane proteins that are important for lipid signaling.^[1] In humans, there are eight LPL receptors, each encoded by a separate gene. These LPL receptor genes are also sometimes referred to as "Edg” (an acronym for endothelial differentiation gene).

Ligands

The ligands for LPL-R group are the lysophospholipid extracellular signaling molecules, lysophosphatidic acid (LPA) and sphingosine 1-phosphate (S1P).

Origin of name

The term lysophospholipid (LPL) refers to any phospholipid that is missing one of its two O-acyl chains. Thus, LPLs have a free alcohol in either the sn-1 or the sn-2 position. The prefix 'lyso-' comes from the fact that lysophospholipids were originally found to be hemolytic, however it is now used to refer generally to phospholipids missing an acyl chain. LPLs are usually the result of phospholipase A-type enzymatic activity on regular phospholipids such as phosphatidylcholine or phosphatidic acid, although they can also be generated by the acylation of glycerophospholipids or the phosphorylation of monoacylglycerols. Some LPLs serve important signaling functions such as lysophosphatidic acid.

Function

LPL receptor ligands bind to and activate their cognate receptors located in the cell membrane. Depending on which ligand, receptor, and cell type is involved, the activated receptor can have a range of effects on the cell. These include primary effects of inhibition of adenylyl cyclase and release of calcium from the endoplasmic reticulum, as well as secondary effects of preventing apoptosis and increasing cell proliferation.^[2]

Group members

The following is a list of the eleven known human LPL receptors:^[1]^[3]^[4]

Gene Symbol	IUPHAR Symbol	Gene / Protein Name	Agonist Ligand	Synonyms
LPAR1	272	lysophosphatidic acid receptor 1	LPA	EDG2
LPAR2	273	lysophosphatidic acid receptor 2	"	EDG4
LPAR3	274	lysophosphatidic acid receptor 3	"	EDG7
LPAR4	LPA₄	lysophosphatidic acid receptor 4	"	GPR23
LPAR5	LPA₅	lysophosphatidic acid receptor 5	"	GPR92
LPAR6	LPA₆	lysophosphatidic acid receptor 6	"	P2RY5
S1PR1	275	sphingosine-1-phosphate receptor 1	S1P	EDG1
S1PR2	276	sphingosine-1-phosphate receptor 2	"	EDG5
S1PR3	277	sphingosine-1-phosphate receptor 3	"	EDG3
S1PR4	278	sphingosine-1-phosphate receptor 4	"	EDG6
S1PR5	279	sphingosine-1-phosphate receptor 5	"	EDG8

References

^ ^a ^b Chun J, Goetzl EJ, Hla T, Igarashi Y, Lynch KR, Moolenaar W, Pyne S, Tigyi G (2002). "International Union of Pharmacology. XXXIV. Lysophospholipid receptor nomenclature". Pharmacol Rev 54 (2): 265–9. doi:10.1124/pr.54.2.265. PMID 12037142.
^ Meyer zu Heringdorf D, Jakobs KH (2007). "Lysophospholipid receptors: signalling, pharmacology and regulation by lysophospholipid metabolism". Biochim Biophys Acta 1768 (4): 923–40. doi:10.1016/j.bbamem.2006.09.026. PMID 17078925.
^ Choi JW, Herr DR, Noguchi K, Yung YC, Lee C-W, Mutoh T, Lin M-E, Teo ST, Park KE, Mosley AN, Chun J (January 2010). "LPA Receptors: Subtypes and Biological Actions". Annual Review of Pharmacology and Toxicology 50 (1): 157–186. doi:10.1146/annurev.pharmtox.010909.105753. PMID 20055701.
^ Pasternack SM, von Kügelgen I, Aboud KA, Lee YA, Rüschendorf F, Voss K, Hillmer AM, Molderings GJ, Franz T, Ramirez A, Nürnberg P, Nöthen MM, Betz RC (March 2008). "G protein-coupled receptor P2Y5 and its ligand LPA are involved in maintenance of human hair growth". Nat. Genet. 40 (3): 329–34. doi:10.1038/ng.84. PMID 18297070.

External links

"Lysophospholipid Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
Lysophospholipid receptors at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 棘状細胞（棘状赤血球および有棘赤血球）と標的細胞の原因 causes of spiculated cells echinocytes and acanthocytes and target cells

English Journal

Extracellular metabolism-dependent uptake of lysolipids through cultured monolayer of differentiated Caco-2 cells.

Inaba M, Murota K, Nikawadori M, Kishino E, Matusda R, Takagi M, Ohkubo T, Tanaka T, Terao J, Tokumura A.Author information Department of Pharmaceutical Health Chemistry, Institute of Health Biosciences, University of Tokushima Graduate School, Japan.AbstractGlycerophospholipids are known to be hydrolyzed in the intestinal lumen into free fatty acids and lysophospholipids that are then absorbed by the intestinal epithelial cells. A monolayer of enterocyte-differentiated Caco-2 cell is often used to assess the intestinal bioavailability of nutrients. In this study, we examined how differentiated Caco-2 cells process lysoglycerolipids such as lysophosphatidylcholine (LPC). Our findings were twofold. (1) Caco-2 cells secreted both a lysophospholipase A-like enzyme and a glycerophosphocholine-phosphodiesterase enzyme into the apical, but not basolateral, lumen, suggesting that food-derived LPC is converted to a free fatty acid, sn-glycerol-3-phosphate, and choline through two sequential enzymatic reactions in humans. The release of the latter enzyme was differentiation-dependent. (2) Fatty acid-releasing activities toward exogenous fluorescent LPC, lysophosphatidic acid and monoacylglycerol were shown to be higher on the apical membranes of Caco-2 cells than on the basolateral membranes. These results suggest that human intestinal epithelial cells metabolize lysoglycerolipids by two distinct mechanisms involving secreted or apical-selective expression of metabolic enzymes.
Biochimica et biophysica acta.Biochim Biophys Acta.2014 Jan;1841(1):121-31. doi: 10.1016/j.bbalip.2013.10.007. Epub 2013 Oct 11.
Glycerophospholipids are known to be hydrolyzed in the intestinal lumen into free fatty acids and lysophospholipids that are then absorbed by the intestinal epithelial cells. A monolayer of enterocyte-differentiated Caco-2 cell is often used to assess the intestinal bioavailability of nutrients. In
PMID 24120920

PLC{varepsilon}, PKD1, and SSH1L Transduce RhoA Signaling to Protect Mitochondria from Oxidative Stress in the Heart.

Xiang SY, Ouyang K, Yung BS, Miyamoto S, Smrcka AV, Chen J, Brown JH.Author information 1Department of Pharmacology, University of California, San Diego, San Diego, CA 92093, USA.AbstractActivation of the small guanosine triphosphatase RhoA can promote cell survival in cultured cardiomyocytes and in the heart. We showed that the circulating lysophospholipid sphingosine 1-phosphate (S1P), a G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR) agonist, signaled through RhoA and phospholipase Cε (PLCε) to increase the phosphorylation and activation of protein kinase D1 (PKD1). Genetic deletion of either PKD1 or its upstream regulator PLCε inhibited S1P-mediated cardioprotection against ischemia/reperfusion injury. Cardioprotection involved PKD1-mediated phosphorylation and inhibition of the cofilin phosphatase Slingshot 1L (SSH1L). Cofilin 2 translocates to mitochondria in response to oxidative stress or ischemia/reperfusion injury, and both S1P pretreatment and SSH1L knockdown attenuated translocation of cofilin 2 to mitochondria. Cofilin 2 associates with the proapoptotic protein Bax, and the mitochondrial translocation of Bax in response to oxidative stress was also attenuated by S1P treatment in isolated hearts or by knockdown of SSH1L or cofilin 2 in cardiomyocytes. Furthermore, SSH1L knockdown, like S1P treatment, increased cardiomyocyte survival and preserved mitochondrial integrity after oxidative stress. These findings reveal a pathway initiated by GPCR agonist-induced RhoA activation, in which PLCε signals to PKD1-mediated phosphorylation of cytoskeletal proteins to prevent the mitochondrial translocation and proapoptotic function of cofilin 2 and Bax and thereby promote cell survival.
Science signaling.Sci Signal.2013 Dec 17;6(306):ra108. doi: 10.1126/scisignal.2004405.
Activation of the small guanosine triphosphatase RhoA can promote cell survival in cultured cardiomyocytes and in the heart. We showed that the circulating lysophospholipid sphingosine 1-phosphate (S1P), a G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR) agonist,
PMID 24345679

The chemical synthesis and cytotoxicity of new sulfur analogues of 2-methoxy-lysophosphatidylcholine.

Rytczak P, Drzazga A, Gendaszewska-Darmach E, Okruszek A.Author information Institute of Technical Biochemistry, Faculty of Biotechnology and Food Sciences, Lodz University of Technology, Stefanowskiego 4/10, 90-924 Lodz, Poland.AbstractThe chemical synthesis of phosphorothioate/phosphorodithioate analogues of 2-methoxy-lysophosphatidylcholine has been described. For the preparation of new sulfur derivatives of lysophosphatidylcholine both oxathiaphospholane and dithiaphospholane approaches have been employed. Each lysophospholipid analogue was synthesized as a series of five compounds, bearing different fatty acid residues both saturated (12:0, 14:0, 16:0, 18:0) and unsaturated (18:1). The methylation of glycerol 2-hydroxyl function was applied in order to increase the stability of prepared analogues by preventing 1→2 acyl migration. The cellular toxicity of newly synthesized 2-methoxy-lysophosphatidylcholine derivatives was measured using MTT viability assay and lactate dehydrogenase release method.
Bioorganic & medicinal chemistry letters.Bioorg Med Chem Lett.2013 Dec 15;23(24):6794-8. doi: 10.1016/j.bmcl.2013.10.020. Epub 2013 Oct 17.
The chemical synthesis of phosphorothioate/phosphorodithioate analogues of 2-methoxy-lysophosphatidylcholine has been described. For the preparation of new sulfur derivatives of lysophosphatidylcholine both oxathiaphospholane and dithiaphospholane approaches have been employed. Each lysophospholipid
PMID 24206765