Department of Cytology and Histology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikatacho, Okayama, 700-8558, Japan.
Mol Cell Biochem. 2010 Jan;333(1-2):137-49. doi: 10.1007/s11010-009-0214-2. Epub 2009 Jul 26.
Phosphatidylserine (PS) externalization is a key feature of apoptotic cell death and plays an important role in clearance of apoptotic cells by phagocytes. PS externalization during apoptosis is generally an irreversible event mediated by caspase activation and is accompanied by other apoptotic events. We report here that an apoptosis inducer alpha-tocopheryl succinate (TOS) can induce PS externalization that is independent of apoptosis and reversible in the absence of fetal bovine serum (FBS) in histiocytic lymphoma U937 cells. In the presence of FBS, TOS induced PS externalization via a caspase-dependent mechanism accompanied by mitochondrial depolarization, cell shrinkage, increase of caspase-3 activity, and chromatin condensation. In contrast, in the absence of FBS, TOS induced the rapid PS externalization which was not accompanied by other apoptotic events. The PS externalization was reversible by removing TOS and was not involved in Ca(2+)-dependent scramblase activation and thiol oxidation of aminophospholipid translocase. A similar PS externalization was also induced by cholesteryl hemisuccinate (CS), the other succinate ester. These results suggested that the mechanism of TOS- and CS-induced PS externalization in the absence of FBS was different from it occurring during typical apoptosis.
磷脂酰丝氨酸（PS）外翻是细胞凋亡的一个关键特征，在吞噬细胞清除凋亡细胞中发挥着重要作用。凋亡过程中的 PS 外翻通常是 caspase 激活介导的不可逆事件，并伴随着其他凋亡事件。我们在这里报告，一种凋亡诱导剂α-生育酚琥珀酸酯（TOS）可以诱导 PS 外翻，这种外翻在组织细胞淋巴瘤 U937 细胞中不依赖于凋亡，并且在没有胎牛血清（FBS）的情况下是可逆的。在 FBS 存在的情况下，TOS 通过依赖 caspase 的机制诱导 PS 外翻，伴随着线粒体去极化、细胞收缩、 caspase-3 活性增加和染色质浓缩。相比之下，在没有 FBS 的情况下，TOS 诱导了快速的 PS 外翻，而不伴随其他凋亡事件。通过去除 TOS，PS 外翻是可逆的，不涉及 Ca(2+)-依赖性翻转酶激活和氨基磷脂移位酶的巯基氧化。类似的 PS 外翻也被胆甾醇半琥珀酸酯（CS）诱导，CS 是另一种琥珀酸酯。这些结果表明，在没有 FBS 的情况下，TOS 和 CS 诱导 PS 外翻的机制与典型凋亡过程中的机制不同。
