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Toxins 2014, 6(3), 1096-1108; doi:10.3390/toxins6031096
Article

Stimulation of Erythrocyte Cell Membrane Scrambling by Mushroom Tyrosinase

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Received: 5 February 2014; in revised form: 24 February 2014 / Accepted: 5 March 2014 / Published: 18 March 2014
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Abstract: Background: Mushroom tyrosinase, a copper containing enzyme, modifies growth and survival of tumor cells. Mushroom tyrosinase may foster apoptosis, an effect in part due to interference with mitochondrial function. Erythrocytes lack mitochondria but are able to undergo apoptosis-like suicidal cell death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine-exposure at the erythrocyte surface. Signaling involved in the triggering of eryptosis include increase of cytosolic Ca2+-activity ([Ca2+]i) and activation of sphingomyelinase with subsequent formation of ceramide. The present study explored, whether tyrosinase stimulates eryptosis. Methods: Cell volume has been estimated from forward scatter, phosphatidylserine-exposure from annexin V binding, [Ca2+]i from Fluo3-fluorescence, and ceramide abundance from binding of fluorescent antibodies in flow cytometry. Results: A 24 h exposure to mushroom tyrosinase (7 U/mL) was followed by a significant increase of [Ca2+]i, a significant increase of ceramide abundance, and a significant increase of annexin-V-binding. The annexin-V-binding following tyrosinase treatment was significantly blunted but not abrogated in the nominal absence of extracellular Ca2+. Tyrosinase did not significantly modify forward scatter. Conclusions: Tyrosinase triggers cell membrane scrambling, an effect, at least partially, due to entry of extracellular Ca2+ and ceramide formation.
Keywords: phosphatidylserine; tyrosinase; calcium; ceramide; cell volume; eryptosis phosphatidylserine; tyrosinase; 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

Frauenfeld, L.; Alzoubi, K.; Abed, M.; Lang, F. Stimulation of Erythrocyte Cell Membrane Scrambling by Mushroom Tyrosinase. Toxins 2014, 6, 1096-1108.

AMA Style

Frauenfeld L, Alzoubi K, Abed M, Lang F. Stimulation of Erythrocyte Cell Membrane Scrambling by Mushroom Tyrosinase. Toxins. 2014; 6(3):1096-1108.

Chicago/Turabian Style

Frauenfeld, Leonie; Alzoubi, Kousi; Abed, Majed; Lang, Florian. 2014. "Stimulation of Erythrocyte Cell Membrane Scrambling by Mushroom Tyrosinase." Toxins 6, no. 3: 1096-1108.



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