Comparative proteomic analysis of cell cycle-dependent apoptosis induced by transforming growth factor-β
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- 作者：Hong-Yu Tian ; Ke-Hua Zhang ; Xia Gao ; Wei-Wei Lei ; Liang Zhang ; Mei-Lan Yu ; Jian-Guo Song ; Fu-Kun Zhao
- 关键词：Proteomics ; Apoptosis ; EMT ; Glutamine synthetase
- 刊名：Biochimica et Biophysica Acta - Proteins and Proteomics
- 出版年：2009
- 出版时间：October 2009
- 年：2009
- 卷：1794
- 期：10
- 页码：1387-1397
- 全文大小：3074 K
文摘
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.