Swainsonine Induces Caprine Luteal Cells Apoptosis via Mitochondrial-Mediated Caspase-Dependent Pathway
Swainsonine Induces Caprine Luteal Cells Apoptosis via Mitochondrial-Mediated Caspase-Dependent Pathway
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DOI：
10.1002/jbt.21585
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发表时间：
2014-10-01
影响因子：
3.6
通讯作者：
Tong, Dewen
中科院分区：
文献类型：
--
作者：
Li, Wei;Huang, Yong;Tong, Dewen
苦马豆素（SW）是从许多有毒植物中分离的吲哚里西啶生物碱。我们以前曾报道SW通过诱导山羊黄体细胞凋亡抑制黄体细胞孕酮的产生，然而，这一现象的分子机制尚不清楚。在这项研究中，SW处理的黄体细胞表现出凋亡的特点，包括核碎裂，DNA梯形的形成，和磷脂酰丝氨酸外化。进一步的研究表明，SW激活caspase-9和caspase-3，随后裂解聚（ADP-核糖）聚合酶。SW还增加Bax/BcL-2的比例，促进Bax从胞质到线粒体的易位，并触发细胞色素c从线粒体释放到细胞质中。而Fas和Fas配体的诱导作用及caspase-8的活性均未出现明显变化。另外的分析还表明，泛半胱天冬酶抑制剂，半胱天冬酶-9抑制剂，或半胱天冬酶-3抑制剂几乎完全保护细胞免受SW诱导的凋亡，但不是半胱天冬酶-8抑制剂。总之，这些数据表明，SW诱导的黄体细胞凋亡，通过垂体介导的半胱天冬酶依赖性途径。
Swainsonine (SW) is an indolizidine alkaloid isolated from a number of poisonous plants. We have previously reported that SW inhibited luteal cell progesterone production by inducing caprine luteal cell apoptosis in vitro; however, the molecular mechanism of this phenomenon remains unclear. In this study, SW-treated luteal cells showed apoptosis characteristics, including nuclear fragmentation, DNA ladder formation, and phosphatidylserine externalization. Further studies showed that SW activated caspase-9 and caspase-3, which subsequently cleaved poly(ADP-ribose) polymerase. SW also increased in Bax/BcL-2 ratios, promoted Bax translocation from the cytosol to mitochondria, and triggered the release of cytochrome c from mitochondria into the cytoplasm. However, Fas and Fas ligand induction or caspase-8 activity did not appear any significant changes. Additional analysis also showed that pan-caspase inhibitor, caspase-9 inhibitor, or caspase-3 inhibitor almost completely protected the cells from SW-induced apoptosis, but not caspase-8 inhibitor. Overall, these data demonstrated that SW induced luteal cells apoptosis through a mitochondrial-mediated caspase-dependent pathway.