Altered expression of signaling genes in Jurkat cells upon FTY720 induced apoptosis.
Altered expression of signaling genes in Jurkat cells upon FTY720 induced apoptosis.
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FTY720 诱导细胞凋亡后 Jurkat 细胞信号基因表达的改变
DOI：
10.3390/ijms11093087
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发表时间：
2010-09-02
影响因子：
5.6
通讯作者：
He S
中科院分区：
文献类型：
--
作者：
Wang F;Tan W;Guo D;Zhu X;Qian K;He S
FTY 720是一种新型的免疫抑制剂，口服后具有显著的降低外周血T淋巴细胞的活性。最近的研究表明，FTY 720对淋巴细胞的作用可能是由于其诱导细胞凋亡的能力。然而，FTY 720诱导细胞凋亡的细胞信号转导机制尚不清楚。在这里，我们研究了凋亡信号通路介导的FTY 720在Jurkat细胞使用微阵列分析。结果表明，FTY 720可诱导Jurkat细胞凋亡，并呈剂量和时间依赖性，细胞存活率、Hoechst 33258染色、Annexin V结合和DNA片段化实验均表明FTY 720可诱导Jurkat细胞凋亡。cDNA微阵列分析显示，10 μM FTY 720孵育6 h后，在Jurkat细胞中检测到的458个凋亡基因中，上调了54个，下调了10个。在微阵列分析中观察到凋亡调节因子-1（MOAP-1）、血管内皮生长因子（VEGF）、肿瘤坏死因子受体相关因子（TRAF 6）、半胱氨酸蛋白酶2（CASP 2）、E2 F转录因子1（E2 F 1）和半胱氨酸蛋白酶5（CASP 5）基因的表达增加至少5倍;这些结果用逆转录聚合酶链反应（RT-PCR）检测证实。我们的研究结果表明，线粒体相关的信号通路参与FTY 720诱导Jurkat细胞凋亡的关键途径。我们的研究结果为FTY 720的作用机制提供了新的见解，这使我们能够绘制第一个简单的图表，显示FTY 720介导的潜在途径。
FTY720, a novel immunosuppressant, has a marked activity in decreasing peripheral blood T lymphocytes upon oral administration. Recent investigations suggest that the action of FTY720 on lymphocytes may result from its ability to induce cell apoptosis. However, the cell signaling mechanism involved in the FTY720-induced cell apoptosis remains unclear. Here we examined the apoptotic signal pathways mediated by FTY720 in Jurkat cells using microarray analysis. The results showed that FTY720 can induce Jurkat cell apoptosis in a dose and time dependent manner as assessed by cell viability, Hoechst 33258 staining, Annexin V binding and DNA fragmentation tests. cDNA microarray analysis showed that 10 μM of FTY720 up-regulated 54 and down-regulated 10 genes in Jurkat cells among the 458 apoptotic genes examined following the 6 h incubation period. At least five-fold increased expression of modulator of apoptosis-1 (MOAP-1), vascular endothelial growth factor (VEGF), tumor necrosis factor receptor-associated factors (TRAF 6), Caspase 2 (CASP 2), E2F transcription factor 1 (E2F 1) and Casapse 5 (CASP 5) genes was observed in microarray analyses; these results were confirmed with reverse transcription polymerase chain reaction (RT-PCR) examination. Our findings suggest that the mitochondria related signaling pathways are the key pathways involved in the FTY720-induced apoptosis in Jurkat cells. And our results provide a new insight into the mechanism of FTY720, which allows us to draw the first simple diagram showing the potential pathways mediated by FTY720.
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影响因子：
64.5
作者：
Du, CY;Fang, M;Wang, XD
通讯作者：
Wang, XD
DOI：
10.1016/s0162-3109(99)00004-1
发表时间：
1999-04-01
期刊：
IMMUNOPHARMACOLOGY
影响因子：
--
作者：
Luo, ZJ;Tanaka, T;Miyasaka, M
通讯作者：
Miyasaka, M
DOI：
10.1073/pnas.0503524102
发表时间：
2005-10-11
影响因子：
11.1
作者：
Tan, KO;Fu, NY;Yu, VC
通讯作者：
Yu, VC
影响因子：
6.4
作者：
Shinomiya, T;Li, XK;Suzuki, S
通讯作者：
Suzuki, S
影响因子：
6.4
作者：
Suzuki, S;Li, XK;Shinomiya, T
通讯作者：
Shinomiya, T