Mitochondria-dependent apoptosis of con A-activated T lymphocytes induced by asiatic acid for preventing murine fulminant hepatitis.
Mitochondria-dependent apoptosis of con A-activated T lymphocytes induced by asiatic acid for preventing murine fulminant hepatitis.
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积雪草酸诱导Con A激活T淋巴细胞线粒体依赖性凋亡预防小鼠暴发性肝炎
DOI：
10.1371/journal.pone.0046018
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Xu Q
中科院分区：
文献类型：
--
作者：
Guo W;Liu W;Hong S;Liu H;Qian C;Shen Y;Wu X;Sun Y;Xu Q
选择性地促进活化T细胞的凋亡对于清除致病性损伤细胞和随后有效解决炎症是必不可少的。然而，很少有化学品被报道在不影响静止T细胞的情况下触发活化T细胞的凋亡以治疗肝炎。在本研究中，我们发现，积雪草酸，一种天然的三萜类化合物，选择性地触发伴刀豆球蛋白A（Con A）激活的T细胞的凋亡，在一个依赖于线粒体的跨膜电位，细胞色素C从线粒体释放到胞质溶胶，半胱天冬酶激活，裂解PARP的破坏指示的细胞凋亡。此外，积雪草酸还能诱导Con A激活的T细胞中Caspase 8和Bid的裂解，增加Fas的表达。然而，活化后的T细胞从MRLlpr/lpr小鼠与Fas突变表现出相似的敏感性，与正常的T细胞相比，积雪草酸诱导的细胞凋亡，表明Fas介导的死亡受体凋亡途径并不主要有助于积雪草酸诱导的细胞死亡。此外，积雪草酸显着减轻刀豆蛋白A诱导的T细胞依赖性暴发性肝炎的小鼠，降低血清转氨酶，促炎细胞因子和病理参数进行评估。与体外实验结果一致，积雪草酸在体内也诱导活化的CD 4 + T细胞凋亡。综上所述，我们的结果表明积雪草酸诱导活化T细胞凋亡的能力及其在治疗T细胞介导的炎性疾病中的潜在用途。
Selectively facilitating apoptosis of activated T cells is essential for the clearance of pathogenic injurious cells and subsequent efficient resolution of inflammation. However, few chemicals have been reported to trigger apoptosis of activated T cells for the treatment of hepatitis without affecting quiescent T cells. In the present study, we found that asiatic acid, a natural triterpenoid, selectively triggered apoptosis of concanavalin A (Con A)-activated T cells in a mitochondria-dependent manner indicated by the disruption of the mitochondrial transmembrane potential, release of cytochrome c from mitochondria to cytosol, caspases activation, and cleavage of PARP. In addition, asiatic acid also induced the cleavage of caspase 8 and Bid and augmented Fas expression in Con A-activated T cells. However, following activation of T cells from MRLlpr/lpr mice with mutation of Fas demonstrated a similar susceptibility to asiatic acid-induced apoptosis compared with normal T cells, suggesting that Fas-mediated death-receptor apoptotic pathway does not mainly contribute to asiatic acid-induced cell death. Furthermore, asiatic acid significantly alleviated Con A-induced T cell-dependent fulminant hepatitis in mice, as assessed by reduced serum transaminases, pro-inflammatory cytokines, and pathologic parameters. Consistent with the in vitro results, asiatic acid also induced apoptosis of activated CD4+ T cells in vivo. Taken together, our results demonstrated that the ability of asiatic acid to induce apoptosis of activated T cells and its potential use in the treatment of T-cell-mediated inflammatory diseases.
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DOI：
10.2174/1566524024605671
发表时间：
2002-05-01
期刊：
Current Molecular Medicine (Hilversum)
影响因子：
--
作者：
Baumann, Sven;Krueger, Andreas;Krammer, Peter H.
通讯作者：
Krammer, Peter H.
影响因子：
15.9
作者：
TIEGS, G;HENTSCHEL, J;WENDEL, A
通讯作者：
WENDEL, A
Saikosaponin a 通过细胞周期停滞和诱导细胞凋亡来抑制 T 细胞的增殖和活化。
影响因子：
5.6
作者：
Sun, Yang;Cai, Tian-Tian;Xu, Qiang
通讯作者：
Xu, Qiang
影响因子：
5
作者：
Kuzuhara, H;Nishiyama, S;Omoto, S
通讯作者：
Omoto, S
影响因子：
4.4
作者：
Xiong, Yuyun;Ding, Hongqun;Gao, Jing
通讯作者：
Gao, Jing