{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T02:22:07Z","timestamp":1768011727456,"version":"3.49.0"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,9,29]],"date-time":"2015-09-29T00:00:00Z","timestamp":1443484800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003329","name":"Ministerio de Econom\u00eda y Competitividad","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2015,12]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The mutated form of the Ca<jats:sup>2+<\/jats:sup> channel <jats:styled-content style=\"fixed-case\">CALHM<\/jats:styled-content>1 (Ca<jats:sup>2+<\/jats:sup> homeostasis modulator 1), P86L\u2010<jats:styled-content style=\"fixed-case\">CALHM<\/jats:styled-content>1, has been correlated with early onset of Alzheimer's disease (<jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>). P86L\u2010<jats:styled-content style=\"fixed-case\">CALHM<\/jats:styled-content>1 increases production of amyloid beta (A\u03b2) upon extracellular Ca<jats:sup>2+<\/jats:sup> removal and its subsequent addback. The aim of this study was to investigate the effect of the overexpression of <jats:styled-content style=\"fixed-case\">CALHM<\/jats:styled-content>1 and P86L\u2010<jats:styled-content style=\"fixed-case\">CALHM<\/jats:styled-content>, upon A\u03b2 treatment, on the following: (i) the intracellular Ca<jats:sup>2+<\/jats:sup> signal pathway; (ii) cell survival proteins <jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content>1\/2 and Ca<jats:sup>2+<\/jats:sup>\/<jats:styled-content style=\"fixed-case\">cAMP<\/jats:styled-content> response element binding (<jats:styled-content style=\"fixed-case\">CREB<\/jats:styled-content>); and (iii) cell vulnerability after treatment with A\u03b2. Using aequorins to measure the effect of nuclear Ca<jats:sup>2+<\/jats:sup> concentrations ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>n<\/jats:sub>) and cytosolic Ca<jats:sup>2+<\/jats:sup> concentrations ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>c<\/jats:sub>) on Ca<jats:sup>2+<\/jats:sup> entry conditions, we observed that baseline [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>n<\/jats:sub> was higher in <jats:styled-content style=\"fixed-case\">CALHM<\/jats:styled-content>1 and P86L\u2010<jats:styled-content style=\"fixed-case\">CALHM<\/jats:styled-content>1 cells than in control cells. Moreover, exposure to A\u03b2 affected [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>c<\/jats:sub> levels in HeLa cells overexpressing <jats:styled-content style=\"fixed-case\">CALHM<\/jats:styled-content>1 and P86L\u2010<jats:styled-content style=\"fixed-case\">CALHM<\/jats:styled-content>1 compared with control cells. Treatment with A\u03b2 elicited a significant decrease in the cell survival proteins p\u2010<jats:styled-content style=\"fixed-case\">ERK<\/jats:styled-content> and p\u2010<jats:styled-content style=\"fixed-case\">CREB<\/jats:styled-content>, an increase in the activity of caspases 3 and 7, and more frequent cell death by inducing early apoptosis in P86L\u2010<jats:styled-content style=\"fixed-case\">CALHM<\/jats:styled-content>1\u2010overexpressing cells than in <jats:styled-content style=\"fixed-case\">CALHM<\/jats:styled-content>1 or control cells. These results suggest that in the presence of A\u03b2, P86L\u2010<jats:styled-content style=\"fixed-case\">CALHM<\/jats:styled-content>1 shifts the balance between neurodegeneration and neuronal survival toward the stimulation of pro\u2010cytotoxic pathways, thus potentially contributing to its deleterious effects in <jats:styled-content style=\"fixed-case\">AD<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/acel.12403","type":"journal-article","created":{"date-parts":[[2015,9,29]],"date-time":"2015-09-29T06:08:14Z","timestamp":1443506894000},"page":"1094-1102","source":"Crossref","is-referenced-by-count":18,"title":["<scp>CALHM<\/scp>1 and its polymorphism P86L differentially control Ca<sup>2+<\/sup> homeostasis, mitogen\u2010activated protein kinase signaling, and cell vulnerability upon exposure to amyloid \u03b2"],"prefix":"10.1111","volume":"14","author":[{"given":"Ana Jos\u00e9","family":"Moreno\u2010Ortega","sequence":"first","affiliation":[{"name":"Servicio de Farmacolog\u00eda Cl\u00ednica Instituto de Investigaci\u00f3n Sanitaria Hospital Universitario de la Princesa Madrid Spain"},{"name":"Instituto Te\u00f3filo Hernando Universidad Aut\u00f3noma de Madrid Madrid Spain"},{"name":"Departamento de Farmacolog\u00eda y Terap\u00e9utica Facultad de Medicina Universidad Aut\u00f3noma de Madrid Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Izaskun","family":"Buendia","sequence":"additional","affiliation":[{"name":"Instituto Te\u00f3filo Hernando Universidad Aut\u00f3noma de Madrid Madrid Spain"},{"name":"Departamento de Farmacolog\u00eda y Terap\u00e9utica Facultad de Medicina Universidad Aut\u00f3noma de Madrid Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lamia","family":"Mouhid","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda y Terap\u00e9utica Facultad de Medicina Universidad Aut\u00f3noma de Madrid Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Javier","family":"Egea","sequence":"additional","affiliation":[{"name":"Servicio de Farmacolog\u00eda Cl\u00ednica Instituto de Investigaci\u00f3n Sanitaria Hospital Universitario de la Princesa Madrid Spain"},{"name":"Instituto Te\u00f3filo Hernando Universidad Aut\u00f3noma de Madrid Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susana","family":"Lucea","sequence":"additional","affiliation":[{"name":"Instituto Te\u00f3filo Hernando Universidad Aut\u00f3noma de Madrid Madrid Spain"},{"name":"Departamento de Farmacolog\u00eda y Terap\u00e9utica Facultad de Medicina Universidad Aut\u00f3noma de Madrid Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Ruiz\u2010Nu\u00f1o","sequence":"additional","affiliation":[{"name":"Servicio de Farmacolog\u00eda Cl\u00ednica Instituto de Investigaci\u00f3n Sanitaria Hospital Universitario de la Princesa Madrid Spain"},{"name":"Instituto Te\u00f3filo Hernando Universidad Aut\u00f3noma de Madrid Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuela G.","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Servicio de Farmacolog\u00eda Cl\u00ednica Instituto de Investigaci\u00f3n Sanitaria Hospital Universitario de la Princesa Madrid Spain"},{"name":"Instituto Te\u00f3filo Hernando Universidad Aut\u00f3noma de Madrid Madrid Spain"},{"name":"Departamento de Farmacolog\u00eda y Terap\u00e9utica Facultad de Medicina Universidad Aut\u00f3noma de Madrid Madrid Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda F.","family":"Cano\u2010Abad","sequence":"additional","affiliation":[{"name":"Servicio de Farmacolog\u00eda Cl\u00ednica Instituto de Investigaci\u00f3n Sanitaria Hospital Universitario de la Princesa Madrid Spain"},{"name":"Instituto Te\u00f3filo Hernando Universidad Aut\u00f3noma de Madrid Madrid 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