α-tocopheryl succinate-induced apoptosis in Jurkat T cells involves caspase-3 activation, and both lysosomal and mitochondrial destabilisation
α-tocopheryl succinate-induced apoptosis in Jurkat T cells involves caspase-3 activation, and both lysosomal and mitochondrial destabilisation
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DOI：
10.1016/s0014-5793(99)00141-6
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发表时间：
1999-02-26
期刊：
影响因子：
3.5
通讯作者：
Brunk, UT
中科院分区：
文献类型：
--
作者：
Neuzil, J;Svensson, I;Brunk, UT
α-生育酚琥珀酸酯（α-TOS），而不是α-生育酚，触发Jurkat T细胞的凋亡。α-TOS以时间和浓度依赖的方式诱导细胞凋亡，在低至30 μ M的α-TOS浓度下，以及在加入酯后3-5小时内，细胞凋亡的迹象是可见的。采用特异性荧光底物，发现响应于50 μ M的α-TOS，胱天蛋白酶-3被迅速激活。我们还发现，当暴露于亲溶酶体弱碱吖啶橙子时，用α-TOS攻击的Jurkat T细胞显示出对染料的溶酶体摄取减少，这表明溶酶体不稳定参与细胞的凋亡。用α-TOS诱导的Jurkat T细胞的凋亡也涉及线粒体膜电位的下降，尽管这种现象发生在溶酶体破裂开始之后。用α-TOS观察到的所有凋亡特征与当Fas受体的交联触发凋亡时发现的那些非常相似。这些发现与最近的观点一致，即维生素E可以通过诱导凋亡来有助于消除恶性细胞，并且可以具有（病理）生理学意义。(C)1999年欧洲生物化学学会联合会。
alpha-Tocopheryl succinate (alpha-TOS), but not alpha-tocopherol, triggered apoptosis in Jurkat T cells. Apoptosis was induced by alpha-TOS in a time- and concentration-dependent mode, and signs of apoptosis were visible at concentrations of alpha-TOS as low as 30 mu M, and within 3-5 h after addition of the ester, Employing a specific fluorogenic substrate, caspase-3 was found to be activated rapidly in response to alpha-TOS at 50 mu M. We also found that Jurkat T cells challenged with alpha-TOS, when exposed to the lysosomotropic weak base acridine orange, showed decreased lysosomal uptake of the dye, This is suggestive of the involvement of lysosomal destabilisation in apoptosis of the cells. Apoptosis of Jurkat T cells induced with alpha-TOS also involved a drop in the mitochondrial membrane potential, although this phenomenon occurred after the initiation of lysosomal rupture. All apoptotic features observed with alpha-TOS were very similar to those found when cross-linking of the Fas receptor triggered apoptosis, These findings are consistent with the recent idea that vitamin E can contribute to elimination of malignant cells by the induction of apoptosis, and can be of (patho)physiological significance. (C) 1999 Federation of European Biochemical Societies.