{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T15:43:08Z","timestamp":1790696588274,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,5,8]],"date-time":"2019-05-08T00:00:00Z","timestamp":1557273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>(1) The beneficial effects of hydrogen sulfide (H2S) on the cardiovascular and nervous system have recently been re-evaluated. It has been shown that lanthionine, a side product of H2S biosynthesis, previously used as a marker for H2S production, is dramatically increased in circulation in uremia, while H2S release is impaired. Thus, lanthionine could be classified as a novel uremic toxin. Our research was aimed at defining the mechanism(s) for lanthionine toxicity. (2) The effect of lanthionine on H2S release was tested by a novel lead acetate strip test (LAST) in EA.hy926 cell cultures. Effects of glutathione, as a redox agent, were assayed. Levels of sulfane sulfur were evaluated using the SSP4 probe and flow cytometry. Protein content and glutathionylation were analyzed by Western Blotting and immunoprecipitation, respectively. Gene expression and miRNA levels were assessed by qPCR. (3) We demonstrated that, in endothelial cells, lanthionine hampers H2S release; reduces protein content and glutathionylation of transsulfuration enzyme cystathionine-\u03b2-synthase; modifies the expression of miR-200c and miR-423; lowers expression of vascular endothelial growth factor VEGF; increases Ca2+ levels. (4) Lanthionine-induced alterations in cell cultures, which involve both sulfur amino acid metabolism and calcium homeostasis, are consistent with uremic dysfunctional characteristics and further support the uremic toxin role of this amino acid.<\/jats:p>","DOI":"10.3390\/ijms20092269","type":"journal-article","created":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T08:19:59Z","timestamp":1557389999000},"page":"2269","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Uremic Toxin Lanthionine Interferes with the Transsulfuration Pathway, Angiogenetic Signaling and Increases Intracellular Calcium"],"prefix":"10.3390","volume":"20","author":[{"given":"Carmela","family":"Vigorito","sequence":"first","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli,\u201d 80131 Naples, Italy"},{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli,\u201d 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evgeniya","family":"Anishchenko","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli,\u201d 80131 Naples, Italy"},{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli,\u201d 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luigi","family":"Mele","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, University of Campania \u201cLuigi Vanvitelli,\u201d 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Capolongo","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli,\u201d 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Trepiccione","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli,\u201d 80131 Naples, Italy"},{"name":"Biogem A. C. S. R. L. Contrada Camporeale, 83031 Ariano Irpino AV, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Zacchia","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli,\u201d 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Lombari","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli,\u201d 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosanna","family":"Capasso","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli,\u201d 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Ingrosso","sequence":"additional","affiliation":[{"name":"Department of Precision Medicine, University of Campania \u201cLuigi Vanvitelli,\u201d 80138 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4048-9392","authenticated-orcid":false,"given":"Alessandra F.","family":"Perna","sequence":"additional","affiliation":[{"name":"Department of Translational Medical Sciences, University of Campania \u201cLuigi Vanvitelli,\u201d 80131 Naples, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16146","DOI":"10.3390\/molecules191016146","article-title":"Hydrogen sulfide and polysulfides as biological mediators","volume":"19","author":"Kimura","year":"2014","journal-title":"Molecules"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1016\/j.niox.2015.02.012","article-title":"Hydrogen sulfide and polysulfides as signaling molecules","volume":"47","author":"Kimura","year":"2015","journal-title":"Nitric Oxide"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"11601","DOI":"10.1074\/jbc.M808026200","article-title":"H2S Biogenesis by Human Cystathionine \u03b3-Lyase Leads to the Novel Sulfur Metabolites Lanthionine and Homolanthionine and Is Responsive to the Grade of Hyperhomocysteinemia","volume":"284","author":"Chiku","year":"2009","journal-title":"J. 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