Mitochondrial toxin betulinic acid induces in vitro eryptosis in human red blood cells through membrane permeabilization
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摘要Betulinic acid (BA), a compound isolated from the bark of white birch (Betula pubescens), was reported to induce apoptosis in many types of cancer through mitochondrial dysfunction with low side effects in normal cells. Because of these features, BA is regarded as a potential anti-cancer agent. However, the effect of BA on the induction of cell death in human erythrocytes remains unknown. Given that BA is a mitochondrial toxin and mitochondria are the central cell death regulator, we hypothesized that BA is unable to elicit apoptosis (also known as eryptosis or erythroptosis) in human erythrocytes devoid of mitochondria. This study therefore tried to determine the in vitro effect of BA on the induction of eryptosis/erythroptosis. Contrary to our prediction, BA caused phosphatidylserine externalization, increase in cellular Ca2+ ion concentration ([Ca2+](i)) and eryptosis/erythroptosis in human erythrocytes with a lethal dose larger than that in cancer lines. Mechanistically, the rise of [Ca2+](i) seems not to be the only key mediator in the BA-mediated eryptosis/erythroptosis because depletion of external Ca2+ and use of Ca2+ channels blockers could not eliminate the BA's effect. Also, BA was able to elicit discocyte-echinocyte transformation and release calcein from the RBC ghosts in a way similar to digitonin through membrane permeabilization. Collectively, we report here for the first time that BA induced eryptosis/erythroptosis in human erythrocytes through Ca2+ loading and membrane permeabilization.
著者Gao MH, Lau PM, Kong SK
期刊名稱Archives of Toxicology
出版年份2014
月份3
日期1
卷號88
期次3
出版社SPRINGER HEIDELBERG
頁次755 - 768
國際標準期刊號0340-5761
電子國際標準期刊號1432-0738
語言英式英語
關鍵詞[Ca2+](i); Betulinic acid; Eryptosis; Erythrocytes; Erythroptosis; Membrane permeabilization
Web of Science 學科類別Toxicology; TOXICOLOGY

上次更新時間 2020-22-10 於 01:36