{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T19:10:33Z","timestamp":1751483433799},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"2","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1997,12,1]]},"abstract":"<jats:p>In this work, we determined the effects of sphingosine 1-phosphate (S1P) on phospholipase D (PLD)-mediated hydrolysis of phosphatidylethanolamine (PtdEtn), and evaluated the effects of the water-soluble product ethanolamine on S1P-induced DNA synthesis in NIH 3T3 cells. In [14C]ethanolamine-labelled cells, S1P (0.5-5 \u03bcM) stimulated PLD-mediated hydrolysis of PtdEtn 1.5-2.1-fold. Down-regulation of protein kinase C by chronic (24 h) treatment of cells with 300 nM PMA, or pretreatments (10 min) with the cell-permeant calcium chelator 1,2-bis-(O-aminophenoxy)-ethane-N,N,N\u02b9,N\u02b9-tetra-acetic acid tetra-acetoxymethyl ester led to the inhibition of S1P-induced PtdEtn hydrolysis. S1P alone was a weak inducer of DNA synthesis, but its effects were enhanced by phosphocholine (PCho), insulin, ATP or PMA. Ethanolamine (5-100 \u03bcM) did not modify the mitogenic effect of S1P alone, whereas at 50-100 \u03bcM concentrations it actually enhanced the mitogenic effect of PCho via a mitogen-activated protein (MAP) kinase-independent mechanism. In contrast, 5-20 \u03bcM concentrations of ethanolamine, which correspond to normal blood ethanolamine levels in humans, strongly inhibited DNA synthesis induced by S1P plus PCho via a MAP kinase-dependent mechanism; importantly, less or no inhibition was observed with 50-100 \u03bcM concentrations of ethanolamine. At 5-50 \u03bcM concentrations, ethanolamine also inhibited the synergistic mitogenic effects of both S1P plus insulin (22-27% inhibition) and PCho plus ATP (45-73% inhibition) but not those of S1P plus PMA or S1P plus ATP. The results indicate that S1P stimulates PLD-mediated hydrolysis of PtdEtn by a mechanism that may involve a regulatory protein kinase C isoform. Increased formation of ethanolamine by PLD-mediated PtdEtn hydrolysis or by other means may be required for maximal stimulation of DNA synthesis by S1P in the presence of insulin, and particularly PCho.<\/jats:p>","DOI":"10.1042\/bj3280383","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T21:57:14Z","timestamp":1439243834000},"page":"383-391","update-policy":"http:\/\/dx.doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Extracellular sphingosine 1-phosphate stimulates formation of ethanolamine from phosphatidylethanolamine: modulation of sphingosine 1-phosphate-induced mitogenesis by ethanolamine"],"prefix":"10.1042","volume":"328","author":[{"given":"Zoltan","family":"KISS","sequence":"first","affiliation":[{"name":"The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S. Karan","family":"CRILLY","sequence":"additional","affiliation":[{"name":"The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. Wayne","family":"ANDERSON","sequence":"additional","affiliation":[{"name":"The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"288","container-title":["Biochemical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/328\/2\/383\/629948\/bj3280383.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/328\/2\/383\/629948\/bj3280383.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:38:38Z","timestamp":1637714318000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/328\/2\/383\/34289\/Extracellular-sphingosine-1-phosphate-stimulates"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1997,12,1]]},"references-count":0,"journal-issue":{"issue":"2","published-print":{"date-parts":[[1997,12,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bj3280383","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[1997,12,1]]}}}