Polyphyllin D induces apoptosis in human erythrocytes through Ca2+ rise and membrane permeabilization

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	Polyphyllin D induces apoptosis in human erythrocytes through Ca2+ rise and membrane permeabilization
	GAO MINGHUI ; CHEUNG K L ; LAU IRENE P ; YU W S ; FUNG K P ; Yu B(俞飚) ; LOO J F ; KONG S K
刊名	Arch. Toxicol.
	2012
卷号	86 期号:5 页码:741-752
ISSN号	0340-5761
其他题名	薯蓣皂苷Polyphyllin D通过Ca2+的上升和膜渗透诱导的人红细胞凋亡
通讯作者	KONG S K
英文摘要	Polyphyllin D (PD) is a potent anticancer agent isolated from a traditional medicinal herb Paris polyphylla that has been used in China for many years to treat cancer. PD is not a substrate of p-glycoprotein, and it can bypass the multi-drug resistance in cancer cell line R-HepG2. However, the effect of PD on the induction of cell death in human erythrocytes remains unknown. Given that PD is a small molecule that can depolarize the mitochondrial membrane potential and release apoptosis-inducing factor (AIF) in isolated mitochondria, we hypothesized that the apoptogenic effect of PD in human erythrocytes devoid of mitochondria would be minimal. This study therefore tried to evaluate the in vitro effect of PD on hemolysis and apoptosis in human erythrocytes. Apoptosis in human red blood cells (RBCs), also known as eryptosis or erythroptosis, after PD treatment was determined by flow cytometry and confocal microscopy for the phosphatidyl-serine externalization and other apoptosis feature events. False to our prediction, PD caused hemolysis and eryptosis/erythroptosis in human RBCs. Mechanistically, elevation in the cytosolic Ca2+ ion level seems to be a key but not the only mediator in the PD-mediated eryptosis/erythroptosis because depletion of the external Ca2+ could not eliminate the PD effect. Also, PD was able to permeabilize the membrane of RBC ghosts in a way similar to digitonin. Taken together, we report here for the first time the toxicity of PD in human RBCs as well as its underlying mechanism for the hemolysis and eryptosis/erythroptosis.
学科主题	生命有机化学
收录类别	SCI
原文出处	http://dx.doi.org/10.1007/s00204-012-0808-4
语种	英语
WOS记录号	WOS:000303346700007
公开日期	2013-08-23
内容类型	期刊论文
源URL	[http://202.127.28.38/handle/331003/28529]
专题	上海有机化学研究所_生命有机化学国家重点实验室
推荐引用方式 GB/T 7714	GAO MINGHUI,CHEUNG K L,LAU IRENE P,et al. Polyphyllin D induces apoptosis in human erythrocytes through Ca2+ rise and membrane permeabilization[J]. Arch. Toxicol.,2012,86(5):741-752.
APA	GAO MINGHUI.,CHEUNG K L.,LAU IRENE P.,YU W S.,FUNG K P.,...&KONG S K.(2012).Polyphyllin D induces apoptosis in human erythrocytes through Ca2+ rise and membrane permeabilization.Arch. Toxicol.,86(5),741-752.
MLA	GAO MINGHUI,et al."Polyphyllin D induces apoptosis in human erythrocytes through Ca2+ rise and membrane permeabilization".Arch. Toxicol. 86.5(2012):741-752.