Mitochondria-dependent apoptosis of activated T lymphocytes induced by astin C, a plant cyclopeptide, for preventing murine experimental colitis
Mitochondria-dependent apoptosis of activated T lymphocytes induced by astin C, a plant cyclopeptide, for preventing murine experimental colitis
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植物环肽 astin C 诱导活化 T 淋巴细胞线粒体依赖性凋亡，用于预防小鼠实验性结肠炎
DOI：
10.1016/j.bcp.2011.04.013
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发表时间：
2011-08-01
影响因子：
5.8
通讯作者：
Xu, Qiang
中科院分区：
文献类型：
--
作者：
Shen, Yan;Luo, Qiong;Xu, Qiang
促进T细胞凋亡被认为是治疗T细胞介导的疾病（包括炎症性肠病）的有效治疗策略。在这里，我们报告说，astin C，从紫菀（菊科）的根中分离的植物环肽，诱导活化的T细胞凋亡的Fas依赖的，但Fas非依赖的方式，这样的活动仍然观察到在T细胞从Fas突变的MRL（lpr/lpr）小鼠。虽然caspase 8没有被激活，但astin C处理导致caspase 9和caspase 3的切割，Bad蛋白表达的上调以及活化T细胞中细胞色素c的释放。Astin C不诱导GRP 78和GADD 153的表达，排除了内质网应激介导的途径。此外，口服给予astin C保护小鼠免受TNBS诱导的结肠炎症，如通过降低的结肠重量/长度比和组织学评分所评估的。给予astin C显著降低了TNF-α、IL-4和IL-17的血清水平，同时诱导体内活化T细胞的凋亡。结果首次证明了astin C诱导活化T细胞凋亡的能力及其在治疗结肠炎症中的潜在用途。(C)2011 Elsevier Inc. All rights reserved.
Facilitating T-cell apoptosis is implicated as an effective therapeutic strategy for treatment of T cell-mediated disease, including inflammatory bowel disease. Here, we report that astin C, a plant cyclopeptide isolated from the roots of Aster tataricus (Compositae), induced apoptosis of activated T cells in a mitochondria-dependent but Fas-independent manner in that such activity was still observed in T cells from Fas-mutated MRL(lpr/lpr) mice. Although caspase 8 was not activated, astin C treatment led to the cleavage of caspase 9 and caspase 3, the upregulation of Bad protein expression as well as release of cytochrome c in activated T cells. Astin C did not induce the expression of GRP78 and GADD153, excluding involvement of endoplasmic reticulum stress-mediated pathway. Moreover, oral administration of astin C protected mice against TNBS-induced colonic inflammation, as assessed by a reduced colonic weight/length ratio and histological scoring. Administering astin C significantly decreased serum levels of TNF-alpha, IL-4 and IL-17, accompanied with the induction of apoptosis in activated T cells in vivo. The results demonstrate, for the first time, the ability of astin C to induce apoptosis in activated T cells and its potential use in the treatment of colonic inflammation. (C) 2011 Elsevier Inc. All rights reserved.