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Toxins 2015, 7(8), 3359-3371; doi:10.3390/toxins7083359

Triggering of Erythrocyte Death by Triparanol

1
Department of Physiology, University of Tübingen, Gmelinstr. 5, 72076 Tuebingen, Germany
2
Department of Biochemistry, Biophysics and General Pathology, School of Medicine and Surgery, Second University of Naples, Via L. De Crecchio 7, 80138 Naples, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Azzam Maghazachi
Received: 22 July 2015 / Revised: 11 August 2015 / Accepted: 12 August 2015 / Published: 24 August 2015
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Abstract

The cholesterol synthesis inhibitor Triparanol has been shown to trigger apoptosis in several malignancies. Similar to the apoptosis of nucleated cells, erythrocytes may enter eryptosis, the suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include oxidative stress which may activate erythrocytic Ca2+ permeable unselective cation channels with subsequent Ca2+ entry and increase of cytosolic Ca2+ activity ([Ca2+]i). The present study explored whether and how Triparanol induces eryptosis. To this end, phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, hemolysis from hemoglobin release, [Ca2+]i from Fluo3-fluorescence, and ROS formation from 2’,7’-dichlorodihydrofluorescein diacetate (DCFDA) dependent fluorescence. As a result, a 48 h exposure of human erythrocytes to Triparanol (20 µM) significantly increased DCFDA fluorescence and significantly increased Fluo3-fluorescence. Triparanol (15 µM) significantly increased the percentage of annexin-V-binding cells, and significantly decreased the forward scatter. The effect of Triparanol on annexin-V-binding was significantly blunted, but not abolished by removal of extracellular Ca2+. In conclusion, Triparanol leads to eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane. Triparanol is at least in part effective by stimulating ROS formation and Ca2+ entry. View Full-Text
Keywords: phosphatidylserine; cell volume; eryptosis; oxidative stress; calcium phosphatidylserine; cell volume; eryptosis; oxidative stress; calcium
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Officioso, A.; Manna, C.; Alzoubi, K.; Lang, F. Triggering of Erythrocyte Death by Triparanol. Toxins 2015, 7, 3359-3371.

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