RGD Reference Report - EDG1 receptor stimulation leads to cardiac hypertrophy in rat neonatal myocytes. - Rat Genome Database

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EDG1 receptor stimulation leads to cardiac hypertrophy in rat neonatal myocytes.

Authors: Robert, P  Tsui, P  Laville, MP  Livi, GP  Sarau, HM  Bril, A  Berrebi-Bertrand, I 
Citation: Robert P, etal., J Mol Cell Cardiol 2001 Sep;33(9):1589-606.
RGD ID: 1357201
Pubmed: PMID:11549339   (View Abstract at PubMed)
DOI: DOI:10.1006/jmcc.2001.1433   (Journal Full-text)

Sphingosine 1 phosphate (S1P), an aminophospholipid, acts extracellularly as a ligand via the specific G protein-coupled receptors of the endothelial differentiation gene (EDG) 1, 3, 5, 6 and 8 receptors family and intracellularly as a second messenger in various cellular types. The aim of this work was to investigate biological activity of S1P in cardiomyocytes with respect to related sphingolipids. S1P was applied for 48 h on rat neonatal cardiomyocytes at 10 nM, 100 nM and 1 microM. S1P induced a concentration-dependent cellular hypertrophy evidenced by an increase in cell size, [3H]-phenylalanine incorporation, protein content and Brain Natriuretic Peptide (BNP) secretion. Among the lipids tested S1P exhibits the lower EC50 (67 nM) followed by dihydro-S1P (107 nM) and sphingosylphosphorylcholine (1.6 microM). The effect of S1P could be related to a stimulation of the EDG1 receptor since we showed that the EDG1 receptor is predominantly expressed at the mRNA and protein levels in rat cardiomyocytes and that specific anti-EDG1 antibodies inhibited the hypertrophic effect induced by S1P. Furthermore the expression level of most other EDG receptors for S1P appeared very low in cardiac myocytes. S1P (100 nM) increased the phosphorylation of p42/44MAPK, p38MAPK, JNK, Akt and p70(S6K), this effect being reversed by inhibitors of their respective phosphorylation which also rescue the hypertrophic phenotype. Finally, S1P stimulated actin stress fibre formation reverted by the Rho inhibitor, the C3 exoenzyme. Altogether, our results show that S1P induces cardiomyocyte hypertrophy mainly via the EDG1 receptor and subsequently via Gi through ERKs, p38 MAPK, JNK, PI3K and via Rho pathway.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Cardiomegaly  ISOS1pr1 (Rattus norvegicus)1357201; 1357201 RGD 
Cardiomegaly  IDA 1357201 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
G protein-coupled receptor signaling pathway  TAS 1357201 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
G protein-coupled receptor activity  TAS 1357201 RGD 

Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cardiac hypertrophy  IMP 1357201 RGD 
Objects Annotated

Genes (Rattus norvegicus)
S1pr1  (sphingosine-1-phosphate receptor 1)

Genes (Mus musculus)
S1pr1  (sphingosine-1-phosphate receptor 1)

Genes (Homo sapiens)
S1PR1  (sphingosine-1-phosphate receptor 1)


Additional Information