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Toxins 2014, 6(5), 1559-1574; doi:10.3390/toxins6051559
Article

In Vitro Induction of Erythrocyte Phosphatidylserine Translocation by the Natural Naphthoquinone Shikonin

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Received: 4 March 2014; in revised form: 5 May 2014 / Accepted: 5 May 2014 / Published: 13 May 2014
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Abstract: Shikonin, the most important component of Lithospermum erythrorhizon, has previously been shown to exert antioxidant, anti-inflammatory, antithrombotic, antiviral, antimicrobial and anticancer effects. The anticancer effect has been attributed to the stimulation of suicidal cell death or apoptosis. Similar to the apoptosis of nucleated cells, erythrocytes may experience eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and by phosphatidylserine translocation to the erythrocyte surface. Triggers of eryptosis include the increase of cytosolic Ca2+-activity ([Ca2+]i) and ceramide formation. The present study explored whether Shikonin stimulates eryptosis. To this end, Fluo 3 fluorescence was measured to quantify [Ca2+]i, forward scatter to estimate cell volume, annexin V binding to identify phosphatidylserine-exposing erythrocytes, hemoglobin release to determine hemolysis and antibodies to quantify ceramide abundance. As a result, a 48 h exposure of human erythrocytes to Shikonin (1 µM) significantly increased [Ca2+]i, increased ceramide abundance, decreased forward scatter and increased annexin V binding. The effect of Shikonin (1 µM) on annexin V binding was significantly blunted, but not abolished by the removal of extracellular Ca2+. In conclusion, Shikonin stimulates suicidal erythrocyte death or eryptosis, an effect at least partially due to the stimulation of Ca2+ entry and ceramide formation.
Keywords: phosphatidylserine; shikonin; calcium; ceramide; cell volume; eryptosis phosphatidylserine; shikonin; calcium; ceramide; cell volume; eryptosis
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.

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MDPI and ACS Style

Lupescu, A.; Bissinger, R.; Jilani, K.; Lang, F. In Vitro Induction of Erythrocyte Phosphatidylserine Translocation by the Natural Naphthoquinone Shikonin. Toxins 2014, 6, 1559-1574.

AMA Style

Lupescu A, Bissinger R, Jilani K, Lang F. In Vitro Induction of Erythrocyte Phosphatidylserine Translocation by the Natural Naphthoquinone Shikonin. Toxins. 2014; 6(5):1559-1574.

Chicago/Turabian Style

Lupescu, Adrian; Bissinger, Rosi; Jilani, Kashif; Lang, Florian. 2014. "In Vitro Induction of Erythrocyte Phosphatidylserine Translocation by the Natural Naphthoquinone Shikonin." Toxins 6, no. 5: 1559-1574.



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