{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T22:22:03Z","timestamp":1789942923611,"version":"4.0.1"},"reference-count":51,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2016,4,8]],"date-time":"2016-04-08T00:00:00Z","timestamp":1460073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2016,4,8]],"date-time":"2016-04-08T00:00:00Z","timestamp":1460073600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100007586","name":"Aix-Marseille Universit\u00e9","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007586","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2016,8]]},"abstract":"Abstract<\/jats:title>\n \n High homocysteine (\n HC<\/jats:styled-content>\n y) levels are associated with lymphocyte\u2010mediated inflammatory responses that are sometimes in turn related to hypoxia. Because adenosine is a potent lymphocyte suppressor produced in hypoxic conditions and shares metabolic pathways with\n HC<\/jats:styled-content>\n y, we addressed the influence of high\n HC<\/jats:styled-content>\n y levels on the hypoxia\u2010induced, adenosine\u2010mediated, alteration of lymphocyte viability. We treated mitogen\u2010stimulated human lymphocytes isolated from healthy individuals and the human lymphoma T\u2010cell line\n CEM<\/jats:styled-content>\n with cobalt chloride (CoCl\n 2<\/jats:sub>\n )to reproduce hypoxia. We found that CoCl\n 2<\/jats:sub>\n \u2010altered cell viability was dose\u2010dependently reversed using\n HC<\/jats:styled-content>\n y. In turn, the\n HC<\/jats:styled-content>\n y effect was inhibited using\n DL<\/jats:styled-content>\n \u2010propargylglycine, a specific inhibitor of the hydrogen sulphide (H\n 2<\/jats:sub>\n S)\u2010synthesizing enzyme cystathionine\u2010\u03b3\u2010lyase involved in\n HC<\/jats:styled-content>\n y catabolism. We then addressed the intracellular metabolic pathway of adenosine and\n HC<\/jats:styled-content>\n y, and the role of the adenosine A\n 2A<\/jats:sub>\n receptor (A\n 2<\/jats:sub>\n \n A<\/jats:sub>\n R\n <\/jats:styled-content>\n ). We observed that: (\n i<\/jats:italic>\n ) hypoxic conditions lowered the intracellular concentration of\n HC<\/jats:styled-content>\n y by increasing adenosine production, which resulted in high A\n 2<\/jats:sub>\n \n A<\/jats:sub>\n R\n <\/jats:styled-content>\n expression and 3\u2032, 5\u2032\u2010cyclic adenosine monophosphate production; (\n ii<\/jats:italic>\n ) increasing intracellular\n HC<\/jats:styled-content>\n y concentration reversed the hypoxia\u2010induced adenosinergic signalling despite high adenosine concentration by promoting both S\u2010adenosylhomocysteine and H\n 2<\/jats:sub>\n S production; (\n iii<\/jats:italic>\n )\n DL<\/jats:styled-content>\n \u2010propargylglycine that inhibits H\n 2<\/jats:sub>\n S production abolished the\n HC<\/jats:styled-content>\n y effect. Together, these data suggest that high\n HC<\/jats:styled-content>\n y levels prevent,\n via<\/jats:italic>\n H\n 2<\/jats:sub>\n S production and the resulting down\u2010regulation of A\n 2<\/jats:sub>\n \n A<\/jats:sub>\n R\n <\/jats:styled-content>\n expression, the hypoxia\u2010induced adenosinergic alteration of lymphocyte viability. We point out the relevance of these mechanisms in the pathophysiology of cardiovascular diseases.\n <\/jats:p>","DOI":"10.1111\/jcmm.12829","type":"journal-article","created":{"date-parts":[[2016,4,10]],"date-time":"2016-04-10T14:36:49Z","timestamp":1460299009000},"page":"1411-1419","source":"Crossref","is-referenced-by-count":16,"title":["High homocysteine levels prevent\n via<\/i>\n H\n 2<\/sub>\n S the CoCl\n 2<\/sub>\n \u2010induced alteration of lymphocyte viability"],"prefix":"10.1111","volume":"20","author":[{"given":"Laurie","family":"Bruzzese","sequence":"first","affiliation":[{"name":"UMR\u2010MD2 Marseille Medical School Aix\u2010Marseille University and IRBA Northern sector Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmanuel","family":"Fenouillet","sequence":"additional","affiliation":[{"name":"UMR\u2010MD2 Marseille Medical School Aix\u2010Marseille University and IRBA Northern sector Marseille France"},{"name":"CNRS Institut des 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