Triptolide induces apoptosis in human leukemia cells through caspase-3-mediated ROCK1 activation and MLC phosphorylation.
Triptolide induces apoptosis in human leukemia cells through caspase-3-mediated ROCK1 activation and MLC phosphorylation.
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雷公藤甲素通过 caspase-3 介导的 ROCK1 激活和 MLC 磷酸化诱导人白血病细胞凋亡
DOI：
10.1038/cddis.2013.469
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发表时间：
2013-12-05
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
雷公藤内酯醇是雷公藤的主要活性成分，雷公藤是一种流行的中草药，具有治疗恶性血液病的潜力。在这项研究中，我们研究了雷公藤内酯醇在人白血病细胞系和原代人白血病母细胞凋亡和细胞信号事件中的作用。雷公藤甲素选择性诱导caspase依赖性细胞死亡，伴随着线粒体膜电位的损失，细胞色素c的释放，和Bax从胞浆易位到线粒体。此外，我们发现雷公藤甲素显着诱导ROCK 1切割/激活和MLC和MYPT磷酸化。ROCK 1被caspase-3切割和激活，而不是RhoA。ML-7抑制MLC磷酸化显著减弱雷公藤内酯醇介导的细胞凋亡、半胱天冬酶激活和细胞色素c释放。此外，ROCK 1抑制还废除了MLC和MYPT磷酸化。我们的体内研究表明，在小鼠白血病异种移植模型中，ROCK 1激活和MLC磷酸化与雷公藤甲素引起的肿瘤生长抑制有关。总的来说，这些研究结果表明，雷公藤内酯醇介导的ROCK 1激活和MLC磷酸化可能是一种新的治疗血液恶性肿瘤的治疗策略。
The diterpene triepoxide triptolide is a major active component of Tripterygium wilfordii Hook F, a popular Chinese herbal medicine with the potential to treat hematologic malignancies. In this study, we investigated the roles of triptolide in apoptosis and cell signaling events in human leukemia cell lines and primary human leukemia blasts. Triptolide selectively induced caspase-dependent cell death that was accompanied by the loss of mitochondrial membrane potential, cytochrome c release, and Bax translocation from the cytosol to the mitochondria. Furthermore, we found that triptolide dramatically induced ROCK1 cleavage/activation and MLC and MYPT phosphorylation. ROCK1 was cleaved and activated by caspase-3, rather than RhoA. Inhibiting MLC phosphorylation by ML-7 significantly attenuated triptolide-mediated apoptosis, caspase activation, and cytochrome c release. In addition, ROCK1 inhibition also abrogated MLC and MYPT phosphorylation. Our in vivo study showed that both ROCK1 activation and MLC phosphorylation were associated with the tumor growth inhibition caused by triptolide in mouse leukemia xenograft models. Collectively, these findings suggest that triptolide-mediated ROCK1 activation and MLC phosphorylation may be a novel therapeutic strategy for treating hematological malignancies.
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影响因子：
4.8
作者：
Kureishi, Y;Kobayashi, S;Ito, M
通讯作者：
Ito, M
影响因子：
12.8
作者：
Li, G.;Zhou, T.;Liu, L.;Chen, J.;Zhao, Z.;Peng, Y.;Li, P.;Gao, N.
通讯作者：
Gao, N.
影响因子：
4
作者：
Miñambres, R;Guasch, RM;Guerri, C
通讯作者：
Guerri, C
影响因子：
20.3
作者：
Carter, Bing Z.;Mak, Duncan H.;Andreeff, Michael
通讯作者：
Andreeff, Michael
Rho-kinase in Vivo的肌球蛋白磷酸酶的肌球蛋白结合亚基（MB）的磷酸化。
DOI：
10.1083/jcb.147.5.1023
发表时间：
1999-11-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kawano Y;Fukata Y;Oshiro N;Amano M;Nakamura T;Ito M;Matsumura F;Inagaki M;Kaibuchi K
通讯作者：
Kaibuchi K