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Publication : Comparative proteomic analysis of cell cycle-dependent apoptosis induced by transforming growth factor-beta.

First Author  Tian HY Year  2009
Journal  Biochim Biophys Acta Volume  1794
Issue  10 Pages  1387-97
PubMed ID  19450710 Mgi Jnum  J:153476
Mgi Id  MGI:4365515 Doi  10.1016/j.bbapap.2009.05.003
Citation  Tian HY, et al. (2009) Comparative proteomic analysis of cell cycle-dependent apoptosis induced by transforming growth factor-beta. Biochim Biophys Acta 1794(10):1387-97
abstractText  Transforming growth factor-beta (TGF-beta) 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-beta at several time points after synchronization in the G2/M or G1/S phase. Upon TGF-beta 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-beta 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-beta-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-beta and how apoptosis and EMT are regulated in the same type of cells.
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