{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T06:08:31Z","timestamp":1773295711976,"version":"3.50.1"},"reference-count":68,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,4,26]],"date-time":"2012-04-26T00:00:00Z","timestamp":1335398400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Loss\u2010of\u2010function mutations in human adenomatous polyposis coli (APC) lead to multiple colonic adenomatous polyps eventually resulting in colonic carcinoma. Similarly, heterozygous mice carrying defective APC (<jats:italic>apc<\/jats:italic><jats:sup>Min\/+<\/jats:sup>) suffer from intestinal tumours. The animals further suffer from anaemia, which in theory could result from accelerated eryptosis, a suicidal erythrocyte death triggered by enhanced cytosolic Ca<jats:sup>2+<\/jats:sup> activity and characterized by cell membrane scrambling and cell shrinkage. To explore, whether APC\u2010deficiency enhances eryptosis, we estimated cell membrane scrambling from annexin V binding, cell size from forward scatter and cytosolic ATP utilizing luciferin\u2013luciferase in isolated erythrocytes from <jats:italic>apc<\/jats:italic><jats:sup>Min\/+<\/jats:sup> mice and wild\u2010type mice (<jats:italic>apc<\/jats:italic><jats:sup>+\/+<\/jats:sup>). Clearance of circulating erythrocytes was estimated by carboxyfluorescein\u2010diacetate\u2010succinimidyl\u2010ester labelling. As a result, <jats:italic>apc<\/jats:italic><jats:sup>Min\/+<\/jats:sup> mice were anaemic despite reticulocytosis. Cytosolic ATP was significantly lower and annexin V binding significantly higher in <jats:italic>apc<\/jats:italic><jats:sup>Min\/+<\/jats:sup> erythrocytes than in <jats:italic>apc<\/jats:italic><jats:sup>+\/+<\/jats:sup> erythrocytes. Glucose depletion enhanced annexin V binding, an effect significantly more pronounced in <jats:italic>apc<\/jats:italic><jats:sup>Min\/+<\/jats:sup> erythrocytes than in <jats:italic>apc<\/jats:italic><jats:sup>+\/+<\/jats:sup> erythrocytes. Extracellular Ca<jats:sup>2+<\/jats:sup> removal or inhibition of Ca<jats:sup>2+<\/jats:sup> entry with amiloride (1 mM) blunted the increase but did not abrogate the genotype differences of annexin V binding following glucose depletion. Stimulation of Ca<jats:sup>2+<\/jats:sup>\u2010entry by treatment with Ca<jats:sup>2+<\/jats:sup>\u2010ionophore ionomycin (10 \u03bcM) increased annexin V binding, an effect again significantly more pronounced in <jats:italic>apc<\/jats:italic><jats:sup>Min\/+<\/jats:sup> erythrocytes than in <jats:italic>apc<\/jats:italic><jats:sup>+\/+<\/jats:sup> erythrocytes. Following retrieval and injection into the circulation of the same mice, <jats:italic>apc<\/jats:italic><jats:sup>Min\/+<\/jats:sup> erythrocytes were more rapidly cleared from circulating blood than <jats:italic>apc<\/jats:italic><jats:sup>+\/+<\/jats:sup> erythrocytes. Most labelled erythrocytes were trapped in the spleen, which was significantly enlarged in <jats:italic>apc<\/jats:italic><jats:sup>Min\/+<\/jats:sup> mice. The observations point to accelerated eryptosis and subsequent clearance of <jats:italic>apc<\/jats:italic><jats:sup>Min\/+<\/jats:sup> erythrocytes, which contributes to or even accounts for the enhanced erythrocyte turnover, anaemia and splenomegaly in those mice.<\/jats:p>","DOI":"10.1111\/j.1582-4934.2011.01387.x","type":"journal-article","created":{"date-parts":[[2011,7,22]],"date-time":"2011-07-22T17:06:24Z","timestamp":1311354384000},"page":"1085-1093","source":"Crossref","is-referenced-by-count":64,"title":["Enhanced suicidal erythrocyte death in mice carrying a loss\u2010of\u2010function mutation of the <i>adenomatous polyposis coli<\/i> gene"],"prefix":"10.1111","volume":"16","author":[{"given":"Syed 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