A recombined protein (rSj16) derived from Schistosoma japonicum induces cell cycle arrest and apoptosis of murine myeloid leukemia cells
A recombined protein (rSj16) derived from Schistosoma japonicum induces cell cycle arrest and apoptosis of murine myeloid leukemia cells
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DOI：
10.1007/s00436-012-3260-8
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发表时间：
2013-01
影响因子：
2
通讯作者：
Fan Yang;Xi Sun;Jia Shen;Li-ping Yu;Jin-yi Liang;Huanquin Zheng;Zhong-dao Wu
中科院分区：
文献类型：
--
作者：
Fan Yang;Xi Sun;Jia Shen;Li-ping Yu;Jin-yi Liang;Huanquin Zheng;Zhong-dao Wu
日本血吸虫重组蛋白rSj 16具有抗炎活性。在这项研究中，我们证明，rSj 16强烈抑制小鼠髓性白血病WEHI-3B JCS细胞的生长，在剂量和时间依赖性的方式。rSj 16通过增加亚G1期凋亡细胞的比例以及使细胞周期停滞在G 0/G1期来诱导凋亡。实时荧光定量PCR检测到细胞周期蛋白D1、D2、D3、E和Cdk 2、4、6基因在WEHI-3B JCS细胞中的表达在24 h时显著下调。4，6-diamidino-2-phenylindole核染色和annexin V/propidium iodide双染色证实rSj 16诱导的细胞凋亡。线粒体膜电位的降低表明线粒体在凋亡过程中的积极参与。rSj 16处理诱导半胱天冬酶3、6和9活性增加以及促凋亡Bax表达。同时，rSj 16处理后，抗凋亡Bcl-2的表达明显降低。以上结果提示，rSj 16通过调控Bcl-2家族的表达，激活caspase介导的机制，诱导小鼠髓性白血病细胞G 0/G1期阻滞和凋亡，从而抑制细胞增殖。
rSj16, a recombined protein fromSchistosoma japonicum, has been identified as an anti-inflammatory molecule. In this study, we demonstrated that rSj16 strongly suppressed the growth of murine myeloid leukemia WEHI-3B JCS cells in a dose- and time-dependent manner. rSj16 induced apoptosis by increasing the proportion of sub-G1 apoptotic cells as well as causing cell cycle arrest at the G0/G1 phase. The expressions of cyclin D1, D2, D3, and E, and Cdk 2, 4, and 6 genes in WEHI-3B JCS cells were significantly down-regulated at 24 h as measured by real-time PCR. Furthermore, apoptosis induced by rSj16 was confirmed by 4,6-diamidino-2-phenylindole nuclear staining assay and annexin V/propidium iodide double staining. A reduction of the mitochondrial membrane potential indicated an active involvement of mitochondria in the apoptosis process. rSj16 treatment induced an increase in the activity of caspase 3, 6, and 9, and expression of pro-apoptotic Bax. Meanwhile, the decreased expression of anti-apoptotic Bcl-2 was observed after rSj16 treatment. Taken together, our results implied that rSj16 can inhibit proliferation by inducing G0/G1 cell cycle arrest and apoptosis of murine myeloid leukemia cells via activation of the caspase-mediated mechanism by regulating the expression of Bcl-2 family.