Abstract：
: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 Ca(2+) ion concentration ([Ca(2+)]i) and eryptosis/erythroptosis in human erythrocytes with a lethal dose larger than that in cancer lines. Mechanistically, the rise of [Ca(2+)]i seems not to be the only key mediator in the BA-mediated eryptosis/erythroptosis because depletion of external Ca(2+) and use of Ca(2+) 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 Ca(2+) loading and membrane permeabilization.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Gao M,Lau PM,Kong SKdoi
10.1007/s00204-013-1162-xsubject
Has Abstractpub_date
2014-03-01 00:00:00pages
755-68issue
3eissn
0340-5761issn
1432-0738journal_volume
88pub_type
杂志文章abstract：:The goal of these studies was to characterize the role played by antigen challenge in 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-induced immunosuppression. The effects of single exposure to TCDD (4.2, 14, and 42 microg/kg) in B6C3F1 mice on the reverse plaque assay (RPA; no sensitization) and the sheep red blood cell ...
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