Swainsonine induces apoptosis through mitochondrial pathway and caspase activation in goat trophoblasts.
Swainsonine induces apoptosis through mitochondrial pathway and caspase activation in goat trophoblasts.
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苦马豆素通过线粒体途径和半胱天冬酶激活诱导山羊滋养层细胞凋亡
DOI：
10.7150/ijbs.9168
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发表时间：
2014
影响因子：
9.2
通讯作者：
Tong D
中科院分区：
文献类型：
--
作者：
Huang Y;Dong F;Du Q;Zhang H;Luo X;Song X;Zhao X;Zhang W;Tong D
吲哚里西啶生物碱苦马豆素（SW）已被报道损害胎盘，并最终导致妊娠山羊流产。然而，SW对山羊滋养层细胞（GTC）的确切作用至今仍不清楚。本研究采用MTT法、AO/EB双染法、DNA片段化法和流式细胞仪检测SW对GTC的细胞毒性作用。结果表明，SW处理显着抑制GTC的活力，并诱导典型的凋亡特征，在时间和浓度依赖性的方式。SW处理增加Bax蛋白水平，降低Bcl-2蛋白水平，诱导Bax易位到线粒体，并触发细胞色素c从线粒体释放到细胞质中，这反过来激活caspase-9和caspase-3，并切割PARP，导致GTC凋亡。而caspase-8活性和Bid水平在SW诱导的细胞凋亡过程中无明显变化。此外，TUNEL法检测表明SW可诱导山羊胎盘子叶GTC凋亡，但对其他细胞无明显影响。综上所述，这些数据表明，SW选择性地诱导GTC细胞凋亡，通过激活细胞凋亡途径介导的山羊胎盘子叶，这可能有助于胎盘功能障碍和流产的妊娠山羊喂养含SW的植物。这些发现为了解SW引起山羊流产的机制提供了新的思路。
The indolizidine alkaloid swainsonine (SW) has been reported to impair placentae and ultimately cause abortion in pregnant goats. Up to now, however, the precise effects of SW on goat trophoblast cells (GTCs) are still unclear. In this study, the cytotoxicity effects of SW on GTCs were detected and evaluated by MTT assay, AO/EB double staining, DNA fragmentation assay and flow cytometry analysis. Results showed that SW treatment significantly suppressed GTCs viability and induced typical apoptotic features in a time- and concentration-dependent manner. SW treatment increased Bax protein levels, reduced Bcl-2 protein levels, induced Bax translocation to mitochondria, and triggered the release of cytochrome c from mitochondria into cytosol, which in turn activated caspase-9 and caspase-3, and cleaved PARP, resulting in GTCs apoptosis. However, caspase-8 activity and the level of Bid did not exhibit significant changes in the process of SW-induced apoptosis. In addition, TUNEL assay suggested that SW induced GTCs apoptosis but not other cells in goat placenta cotyledons. Taken together, these data suggest that SW selectively induces GTCs apoptosis via the activation of mitochondria-mediated apoptosis pathway in goat placenta cotyledons, which might contribute to placentae impairment and abortion in pregnant goats fed with SW-containing plants. These findings may provide new insights to understand the mechanisms involved in SW-caused goat's abortion.
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影响因子：
5.6
作者：
Doi K;Ishigami N;Sehata S
通讯作者：
Sehata S
影响因子：
--
作者：
Sehata, S;Kiyosawa, N;Doi, K
通讯作者：
Doi, K
苦马豆素通过激活线粒体途径在体外和体内促进人食管鳞状细胞癌细胞凋亡
影响因子：
2.9
作者：
Li, Zhaocai;Huang, Yong;Tong, Dewen
通讯作者：
Tong, Dewen
苦马豆素对体外山羊黄体细胞的类固醇生成和活力有不同影响
影响因子：
2.8
作者：
Huang, Yong;Li, Wei;Tong, Dewen
通讯作者：
Tong, Dewen
影响因子：
3.8
作者：
Huppertz, B;Hemmings, D;Chamley, LW
通讯作者：
Chamley, LW