Sphingosine-1-phosphate induces proliferation of astrocytes: regulation by intracellular signalling cascades
Autor: | Alice Pébay, Toutant, M., Prémont, J., Calvo, C. -F, Venance, L., Cordier, J., Glowinski, J., Tencé, M. |
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Přispěvatelé: | Transduction du Signal et Plasticite Dans Le Systeme Nerveux, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Dynamic and Pathophysiology of Neuronal Networks, center for interdisciplinarity Research in Biology, Collège de France - Chaire Neuropharmacologie (INSERM U114), Collège de France (CdF (institution)), Laboratoire de Physique des Solides (LPS), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Chaire Neuropharmacologie (INSERM U114) |
Jazyk: | angličtina |
Rok vydání: | 2001 |
Předmět: |
calcium
extracellular signal-regulated kinase (Erk) proliferation [SDV]Life Sciences [q-bio] [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology lipids (amino acids peptides and proteins) cyclic AMP [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] phospholipase C mouse Edg receptors |
Zdroj: | European Journal of Neuroscience European Journal of Neuroscience, 2001, 13 (12), pp.2067-76. ⟨10.1046/j.0953-816x.2001.01585.x⟩ Scopus-Elsevier European Journal of Neuroscience, Wiley, 2001, 13 (12), pp.2067-76. ⟨10.1046/j.0953-816x.2001.01585.x⟩ |
ISSN: | 0953-816X 1460-9568 |
DOI: | 10.1046/j.0953-816x.2001.01585.x⟩ |
Popis: | International audience; 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 S1P 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. |
Databáze: | OpenAIRE |
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