Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
49
pubmed:dateCreated
2001-1-18
pubmed:abstractText
Lysophosphatidic acid (LPA)-mediated Ca(2+) mobilization in human SH-SY5Y neuroblastoma cells does not involve either inositol 1,4, 5-trisphosphate (Ins(1,4,5)P(3))- or ryanodine-receptor pathways, but is sensitive to inhibitors of sphingosine kinase. This present study identifies Edg-4 as the receptor subtype involved and investigates the presence of a Ca(2+) signaling cascade based upon the lipid second messenger molecule, sphingosine 1-phosphate. Both LPA and direct G-protein activation increase [(3)H]sphingosine 1-phosphate levels in SH-SY5Y cells. Measurements of (45)Ca(2+) release in premeabilized SH-SY5Y cells indicates that sphingosine 1-phosphate, sphingosine, and sphingosylphosphorylcholine, but not N-acetylsphingosine are capable of mobilizing intracellular Ca(2+). Furthermore, the effect of sphingosine was attenuated by the sphingosine kinase inhibitor dimethylsphingosine, or removal of ATP. Confocal microscopy demonstrated that LPA stimulated intracellular Ca(2+) "puffs," which resulted from an interaction between the sphingolipid Ca(2+) release pathway and Ins(1,4,5)P(3) receptors. Down-regulation of Ins(1,4,5)P(3) receptors uncovered a Ca(2+) response to LPA, which was manifest as a progressive increase in global cellular Ca(2+) with no discernible foci. We suggest that activation of an LPA-sensitive Edg-4 receptor solely utilizes the production of intracellular sphingosine 1-phosphate to stimulate Ca(2+) mobilization in SH-SY5Y cells. Unlike traditional Ca(2+) release processes, this novel pathway does not require the progressive recruitment of elementary Ca(2+) events.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Caffeine, http://linkedlifedata.com/resource/pubmed/chemical/Calcium, http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels, http://linkedlifedata.com/resource/pubmed/chemical/Guanosine 5'-O-(3-Thiotriphosphate), http://linkedlifedata.com/resource/pubmed/chemical/Heterotrimeric GTP-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/ITPR1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate, http://linkedlifedata.com/resource/pubmed/chemical/Inositol 1,4,5-Trisphosphate..., http://linkedlifedata.com/resource/pubmed/chemical/Lysophospholipids, http://linkedlifedata.com/resource/pubmed/chemical/N,N-dimethylsphingosine, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cytoplasmic and Nuclear, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, G-Protein-Coupled, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Lysophosphatidic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Sphingosine, http://linkedlifedata.com/resource/pubmed/chemical/sphingosine 1-phosphate
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
8
pubmed:volume
275
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
38532-9
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10954727-Caffeine, pubmed-meshheading:10954727-Calcium, pubmed-meshheading:10954727-Calcium Channels, pubmed-meshheading:10954727-Calcium Signaling, pubmed-meshheading:10954727-Guanosine 5'-O-(3-Thiotriphosphate), pubmed-meshheading:10954727-Heterotrimeric GTP-Binding Proteins, pubmed-meshheading:10954727-Humans, pubmed-meshheading:10954727-Inositol 1,4,5-Trisphosphate, pubmed-meshheading:10954727-Inositol 1,4,5-Trisphosphate Receptors, pubmed-meshheading:10954727-Kinetics, pubmed-meshheading:10954727-Lysophospholipids, pubmed-meshheading:10954727-Neuroblastoma, pubmed-meshheading:10954727-Receptors, Cell Surface, pubmed-meshheading:10954727-Receptors, Cytoplasmic and Nuclear, pubmed-meshheading:10954727-Receptors, G-Protein-Coupled, pubmed-meshheading:10954727-Receptors, Lysophosphatidic Acid, pubmed-meshheading:10954727-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:10954727-Sphingosine, pubmed-meshheading:10954727-Tumor Cells, Cultured
pubmed:year
2000
pubmed:articleTitle
Lysophosphatidic acid-induced Ca2+ mobilization requires intracellular sphingosine 1-phosphate production. Potential involvement of endogenous EDG-4 receptors.
pubmed:affiliation
Department of Cell Physiology and Pharmacology, Medical Sciences Building, University of Leicester, University Road, Leicester, LE1 9HN United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't