Comparative proteomic analysis of cell cycle-dependent apoptosis induced by transforming growth factor-beta.
Comparative proteomic analysis of cell cycle-dependent apoptosis induced by transforming growth factor-beta.
复制标题
转化生长因子-β 诱导的细胞周期依赖性细胞凋亡的比较蛋白质组学分析。
DOI：
10.1016/j.bbapap.2009.05.003
复制
发表时间：
2009-10
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
转化生长因子-β（transforminggrowthfactor-β，TGF-β）可诱导肝细胞发生G2/M期依赖的凋亡和G1/S期依赖的上皮-间质转化（epithelial-mesenchymaltransition，EMT），但其机制尚不清楚。在这项研究中，我们使用二维凝胶电泳研究了AML-12小鼠肝细胞在G2/M或G1/S期同步化后的几个时间点用TGF-β处理后的整体蛋白质组的变化。经TGF-β处理后，G2/M期细胞中44种蛋白的表达水平发生了显著变化。通过MALDI-TOF/TOF技术对这些蛋白质进行鉴定，并根据功能将其分为7类。此外，TGF-β诱导G2/M期细胞谷氨酰胺合成酶表达下调，而G1/S期细胞谷氨酰胺合成酶表达无明显变化，免疫印迹进一步证实了这一点。此外，外源性谷氨酰胺可完全阻断TGF-β诱导的G2/M期和非同步化细胞凋亡，而对EMT无影响，提示谷氨酰胺合成酶的下调参与了G2/M期依赖的细胞凋亡。这些结果为TGF-β的多功能作用机制以及凋亡和EMT在同一类型细胞中的调节提供了新的见解。
Transforming growth factor-β (TGF-β) can induce G2/M phase-dependent apoptosis and G1/S phase-dependent epithelial–mesenchymal transition (EMT) in hepatocytes, but the underlying mechanism remains poorly understood. In this study, we investigated alterations in the global proteome using two dimensional gel electrophoresis of AML-12 murine hepatocyte cells after treatment with TGF-β at several time points after synchronization in the G2/M or G1/S phase. Upon TGF-β treatment, the expression levels of 44 proteins were found to be significantly changed in cells synchronized in the G2/M phase. These proteins were identified by MALDI-TOF/TOF and classified into seven categories according to function. In addition, TGF-β induced downregulation of glutamine synthetase in cells in G2/M but not G1/S phase, and this was further confirmed by immunoblotting. Moreover, exogenous glutamine completely blocked TGF-β-induced apoptosis in G2/M and non-synchronized cells, whereas it had no effect on EMT, suggesting that the downregulation of glutamine synthetase is involved in G2/M phase-dependent apoptosis. These results provide new insight into the mechanism of the multifunctional effects of TGF-β and how apoptosis and EMT are regulated in the same type of cells.
登录
查看更多内容
影响因子：
8
作者：
Y. Yang;X. Pan;W. Lei;J. Wang;J. Song
通讯作者：
Y. Yang;X. Pan;W. Lei;J. Wang;J. Song
DOI：
10.13039/501100004587
发表时间：
1983-08
期刊：
--
影响因子：
--
作者：
Cristina Rodríguez;Tomás Sobrino;José Carlos Gómez Sánchez;Angeles Almeida
通讯作者：
Cristina Rodríguez;Tomás Sobrino;José Carlos Gómez Sánchez;Angeles Almeida
影响因子：
4.2
作者：
N. Schuster;Herdis Bender;O. G. Rössler;A. Philippi;N. Dünker;G. Thiel;K. Krieglstein
通讯作者：
N. Schuster;Herdis Bender;O. G. Rössler;A. Philippi;N. Dünker;G. Thiel;K. Krieglstein
影响因子：
4.8
作者：
Mehlen, P;SchulzeOsthoff, K;Arrigo, AP
通讯作者：
Arrigo, AP
影响因子：
4.8
作者：
Ko, YG;Kim, EK;Kim, S
通讯作者：
Kim, S