{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T12:25:26Z","timestamp":1754396726854},"reference-count":0,"publisher":"Portland Press Ltd.","issue":"1","content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[1995,10,1]]},"abstract":"<jats:p>We previously reported that difluoromethylornithine (DFMO), an inhibitor of polyamine biosynthesis, exerted significant beneficial effects on the lifespan and disease expression of MRL-lpr\/lpr mice, which spontaneously develop a lupus-like syndrome. Polyamine levels in splenic T-cells of MRL-lpr\/lpr mice were significantly higher than those of Balb\/c mice. In the present investigation, we examined the role of endogenous polyamines in transmembrane Ca2+ influx, generation of InsP3 and tyrosine phosphorylation of the p56lck protein in concanavalin A-stimulated splenic T-cells. Cytosolic free calcium concentrations ([Ca2+]i) in concanavalin A-stimulated T-cells of MRL-lpr\/lpr and Balb\/c mice were 250 +\/- 25 and 450 +\/- 42 nM respectively. Treatment of MRL-lpr\/lpr mice with DFMO increased [Ca2+]i to 360 +\/- 30 nM (P &amp;lt; 0.05). InsP3 levels of concanavalin A-stimulated MRL-lpr\/lpr splenic T-cells were only 20% higher than those of unstimulated controls, whereas those of Balb\/c T-cells were 90% higher. DFMO treatment increased InsP3 levels in concanavalin A-treated MRL-lpr\/lpr T-cells to 67%. Western-blot analysis showed a 7-fold higher level of p56lck phosphorylation of MRL-lpr\/lpr splenic T-cells than that of Balb\/c mice. DFMO treatment reduced tyrosine phosphorylation of p56lck of MRL-lpr\/lpr mice significantly (P &amp;lt; 0.001). Two-colour flow-cytometric analysis revealed no significant difference in the CD4+\/CD8+ ratio in splenic T-cells of MRL-lpr\/lpr mice after DFMO treatment. Polyamine levels in splenocytes were significantly reduced by DFMO treatment. These data show that DFMO treatment could alter signal-transduction pathways of splenic T-cells of MRL-lpr\/lpr mice. Increased levels of polyamines in T-cells of untreated lpr mice contribute to defective signal-transduction pathways and the pathogenesis of lupus-like symptoms.<\/jats:p>","DOI":"10.1042\/bj3110175","type":"journal-article","created":{"date-parts":[[2015,8,10]],"date-time":"2015-08-10T21:45:43Z","timestamp":1439243143000},"page":"175-182","update-policy":"http:\/\/dx.doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Defective signal-transduction pathways in T-cells from autoimmune MRL-<i>lpr\/lpr<\/i> mice are associated with increased polyamine concentrations"],"prefix":"10.1042","volume":"311","author":[{"given":"T J","family":"Thomas","sequence":"first","affiliation":[{"name":"Clinical Research Center and the Departments of Medicine and Environmental and Community Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"U B","family":"Gunnia","sequence":"additional","affiliation":[{"name":"Clinical Research Center and the Departments of Medicine and Environmental and Community Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J R","family":"Seibold","sequence":"additional","affiliation":[{"name":"Clinical Research Center and the Departments of Medicine and Environmental and Community Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, U.S.A."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T","family":"Thomas","sequence":"additional","affiliation":[{"name":"Clinical Research Center and the Departments of Medicine and Environmental and Community Medicine, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, 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\/311\/1\/175\/618164\/bj3110175.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/biochemj\/article-pdf\/311\/1\/175\/618164\/bj3110175.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T23:43:38Z","timestamp":1637711018000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/biochemj\/article\/311\/1\/175\/32001\/Defective-signal-transduction-pathways-in-T-cells"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,10,1]]},"references-count":0,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1995,10,1]]}},"URL":"https:\/\/doi.org\/10.1042\/bj3110175","relation":{},"ISSN":["0264-6021","1470-8728"],"issn-type":[{"value":"0264-6021","type":"print"},{"value":"1470-8728","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,10,1]]}}}