Antiproliferative properties of sphingosine-1-phosphate in human hepatic myofibroblasts

被引:115
作者
Pébay, A
Toutant, M
Prémont, J
Calvo, CF
Venance, L
Cordier, J
Glowinski, J
Tencé, M
机构
[1] Coll France, INSERM, U114, Chaire Neuropharmacol, F-75231 Paris 05, France
[2] Inst Fer Moulin, INSERM, U536, F-75005 Paris, France
关键词
calcium; cyclic AMP; Edg receptors; extracellular signal-regulated kinase (Erk); mouse; phospholipase C; proliferation;
D O I
10.1046/j.0953-816x.2001.01585.x
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Sphingosine-1-phosphate (S1P) is a potent lysophospholipid mediator mostly released by activated platelets. It is involved in several functions in peripheral tissues. but its effects in the central nervous system are poorly documented. Therefore, we have examined the effects of S1P on the proliferation of striatal astrocytes from the mouse embryo. These cells have been found to express mRNAs for the S1P receptors, Edg-1 and Edg-3. S1P stimulated thymidine incorporation and induced activation of extracellular signal-regulated kinases (Erks). Both effects were prevented by U0126, an Erk kinase inhibitor. The S1P-evoked activation of Erk1 was totally blocked in astrocytes pretreated with a combination of either phorbol ester (24 h) and LY294002, or phorbol ester (24 h) and pertussis toxin (PTX). Each individual treatment only partially inhibited Erk1 activation. This suggests that several separate mechanisms mediate this process, one involving protein kinase C and another involving Gi/Go proteins and phosphatidylinositol 3-kinase. In contrast, the stimulatory effect of SIP on astrocyte proliferation was totally blocked by either PTX or LY294002, but not by a downregulation of protein kinase C. S1P dramatically inhibited the evoked production of cyclic AMP, a response that was impaired by PTX. Finally, S1P stimulated the production of inositol phosphates and increased intracellular calcium by mobilization from thapsigargin-sensitive stores. These latter effects were mainly insensitive to PTX. Probably, Gi/Go protein activation and phosphoinositide hydrolysis are early events that regulate the activation of Erks by S1P. Altogether, these observations show that astrocytes are targets for S1P. Their proliferation in response to S1P could have physiopathological consequences at sites of brain lesions and alterations of the blood-brain barrier.
引用
收藏
页码:2067 / 2076
页数:10
相关论文
共 59 条
  • [31] Nrg-1 belongs to the endothelial differentiation gene family of G protein-coupled sphingosime-1-phosphate receptors
    Malek, RL
    Toman, RE
    Edsall, LC
    Wong, S
    Chiu, J
    Letterle, CA
    Van Brocklyn, JR
    Milstien, S
    Spiegel, S
    Lee, NH
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (08) : 5692 - 5699
  • [32] Bioactive lysophospholipids and their G protein-coupled receptors
    Moolenaar, WH
    [J]. EXPERIMENTAL CELL RESEARCH, 1999, 253 (01) : 230 - 238
  • [33] Sphingosine-1-phosphate induces apoptosis of cultured hippocampal neurons that requires protein phosphatases and activator protein-1 complexes
    Moore, AN
    Kampfl, AW
    Zhao, X
    Hayes, RL
    Dash, PK
    [J]. NEUROSCIENCE, 1999, 94 (02) : 405 - 415
  • [34] Quantitative measurement of sphingosine 1-phosphate by radioreceptor-binding assay
    Murata, N
    Sato, K
    Ken, J
    Tomura, H
    Okajima, F
    [J]. ANALYTICAL BIOCHEMISTRY, 2000, 282 (01) : 115 - 120
  • [35] Expression of norepinephrine and serotonin transporter mRNAs in the rat superior cervical ganglion
    Nishimura, M
    Sato, K
    Shimada, S
    Tohyama, M
    [J]. MOLECULAR BRAIN RESEARCH, 1999, 67 (01): : 82 - 86
  • [36] EDG3 is a functional receptor specific for sphingosine 1-phosphate and sphingosylphosphorylcholine with signaling characteristics distinct from EDG1 and AGR16
    Okamoto, H
    Takuwa, N
    Yatomi, Y
    Gonda, K
    Shigematsu, H
    Takuwa, Y
    [J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1999, 260 (01) : 203 - 208
  • [37] EDG1 is a functional sphingosine-l-phosphate receptor that is linked via a Gi/o to multiple signaling pathways, including phospholipase C activation, Ca2+ mobilization, Ras-mitogen-activated protein kinase activation, and adenylate cyclase inhibition
    Okamoto, H
    Takuwa, N
    Gonda, K
    Okazaki, H
    Chang, K
    Yatomi, Y
    Shigematsu, H
    Takuwa, Y
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (42) : 27104 - 27110
  • [38] Pébay A, 1999, GLIA, V28, P25, DOI 10.1002/(SICI)1098-1136(199910)28:1<25::AID-GLIA3>3.0.CO
  • [39] 2-D
  • [40] Sphingosine-1-phosphate rapidly induces Rho-dependent neurite retraction: Action through a specific cell surface receptor
    Postma, FR
    Jalink, K
    Hengeveld, T
    Moolenaar, WH
    [J]. EMBO JOURNAL, 1996, 15 (10) : 2388 - 2392