Lysophosphatidic Acid Stimulates Astrocyte Proliferation Through LPA1

Overview

Journal Neurochem Int

Specialties Chemistry
Neurology

Date 2007 Aug 19

PMID 17692995

Citations 37

Authors

Shinya Shano

Ryutaro Moriyama

Jerold Chun

Nobuyuki Fukushima

Affiliations

Soon will be listed here.

Abstract

Lysophosphatidic acid (LPA) is an extracellular lipid mediator that regulates nervous system development and functions through multiple types of LPA receptors. Here we explore the role of LPA receptor subtypes in cortical astrocyte functions. Astrocytes cultured under serum-free conditions were found to express the genes of five LPA receptor subtypes, lpa1 to lpa5. When astrocytes were treated with dibutyryl cyclic adenosine monophosphate, a reagent inducing astrocyte differentiation or activation, lpa1 expression levels remained unchanged, but those of other LPA receptor subtypes were relatively reduced. LPA stimulated DNA synthesis in both undifferentiated and differentiated astrocytes, but failed to do so in astrocytes prepared from mice lacking lpa1 gene. LPA also inhibited [3H]-glutamate uptake in both undifferentiated and differentiated astrocytes; and LPA-induced inhibition of glutamate uptake was still observed in lpa1-deficient astrocytes. Taken together, these observations demonstrate that LPA1 mediates LPA-induced stimulation of cell proliferation but not inhibition of glutamate uptake in astrocytes.

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References

Noguchi K, Ishii S, Shimizu T . Identification of p2y9/GPR23 as a novel G protein-coupled receptor for lysophosphatidic acid, structurally distant from the Edg family. J Biol Chem. 2003; 278(28):25600-6. DOI: 10.1074/jbc.M302648200. View

Stankoff B, Barron S, Allard J, Barbin G, Noel F, Aigrot M . Oligodendroglial expression of Edg-2 receptor: developmental analysis and pharmacological responses to lysophosphatidic acid. Mol Cell Neurosci. 2002; 20(3):415-28. DOI: 10.1006/mcne.2002.1129. View

Sorensen S, Nicole O, Peavy R, Montoya L, Lee C, Murphy T . Common signaling pathways link activation of murine PAR-1, LPA, and S1P receptors to proliferation of astrocytes. Mol Pharmacol. 2003; 64(5):1199-209. DOI: 10.1124/mol.64.5.1199. View

Kingsbury M, K Rehen S, Contos J, Higgins C, Chun J . Non-proliferative effects of lysophosphatidic acid enhance cortical growth and folding. Nat Neurosci. 2003; 6(12):1292-9. DOI: 10.1038/nn1157. View

Ishii I, Fukushima N, Ye X, Chun J . Lysophospholipid receptors: signaling and biology. Annu Rev Biochem. 2004; 73:321-54. DOI: 10.1146/annurev.biochem.73.011303.073731. View

Sensenbrenner M, Devilliers G, Bock E, Porte A . Biochemical and ultrastructural studies of cultured rat astroglial cells: effect of brain extract and dibutyryl cyclic AMP on glial fibrillary acidic protein and glial filaments. Differentiation. 1980; 17(1):51-61. DOI: 10.1111/j.1432-0436.1980.tb01081.x. View

Eichholtz T, Jalink K, Fahrenfort I, Moolenaar W . The bioactive phospholipid lysophosphatidic acid is released from activated platelets. Biochem J. 1993; 291 ( Pt 3):677-80. PMC: 1132420. DOI: 10.1042/bj2910677. View

Tigyi G, Hong L, Yakubu M, Parfenova H, Shibata M, Leffler C . Lysophosphatidic acid alters cerebrovascular reactivity in piglets. Am J Physiol. 1995; 268(5 Pt 2):H2048-55. DOI: 10.1152/ajpheart.1995.268.5.H2048. View

Keller J, Steiner M, Mattson M, Steiner S . Lysophosphatidic acid decreases glutamate and glucose uptake by astrocytes. J Neurochem. 1996; 67(6):2300-5. DOI: 10.1046/j.1471-4159.1996.67062300.x. View

10.

Swanson R, Liu J, Miller J, Rothstein J, Farrell K, Stein B . Neuronal regulation of glutamate transporter subtype expression in astrocytes. J Neurosci. 1997; 17(3):932-40. PMC: 6573161. View

11.

Gegelashvili G, Schousboe A . High affinity glutamate transporters: regulation of expression and activity. Mol Pharmacol. 1997; 52(1):6-15. DOI: 10.1124/mol.52.1.6. View

12.

Keller J, Steiner M, Holtsberg F, Mattson M, Steiner S . Lysophosphatidic acid-induced proliferation-related signals in astrocytes. J Neurochem. 1997; 69(3):1073-84. DOI: 10.1046/j.1471-4159.1997.69031073.x. View

13.

Schlag B, Vondrasek J, Munir M, Kalandadze A, Zelenaia O, Rothstein J . Regulation of the glial Na+-dependent glutamate transporters by cyclic AMP analogs and neurons. Mol Pharmacol. 1998; 53(3):355-69. DOI: 10.1124/mol.53.3.355. View

14.

Weiner J, Hecht J, Chun J . Lysophosphatidic acid receptor gene vzg-1/lpA1/edg-2 is expressed by mature oligodendrocytes during myelination in the postnatal murine brain. J Comp Neurol. 1998; 398(4):587-98. View

15.

Pebay A, Torrens Y, Toutant M, Cordier J, Glowinski J, Tence M . Pleiotropic effects of lysophosphatidic acid on striatal astrocytes. Glia. 1999; 28(1):25-33. DOI: 10.1002/(sici)1098-1136(199910)28:1<25::aid-glia3>3.0.co;2-d. View

16.

Schousboe A, Waagepetersen H . Role of astrocytes in glutamate homeostasis: implications for excitotoxicity. Neurotox Res. 2005; 8(3-4):221-5. DOI: 10.1007/BF03033975. View

17.

Lee C, Rivera R, Gardell S, Dubin A, Chun J . GPR92 as a new G12/13- and Gq-coupled lysophosphatidic acid receptor that increases cAMP, LPA5. J Biol Chem. 2006; 281(33):23589-97. DOI: 10.1074/jbc.M603670200. View

18.

Moolenaar W . Bioactive lysophospholipids and their G protein-coupled receptors. Exp Cell Res. 1999; 253(1):230-8. DOI: 10.1006/excr.1999.4702. View

19.

Fuentes E, Nadal A, McNaughton P . Lysophospholipids trigger calcium signals but not DNA synthesis in cortical astrocytes. Glia. 1999; 28(3):272-6. View

20.

Fukushima N, Shano S, Moriyama R, Chun J . Lysophosphatidic acid stimulates neuronal differentiation of cortical neuroblasts through the LPA1-G(i/o) pathway. Neurochem Int. 2006; 50(2):302-7. DOI: 10.1016/j.neuint.2006.09.008. View