Summary
To investigate the effect of lithium on cell cycle progression of airway epithelial cells, primary pig tracheobronchial epithelial cells were incubated with lithium chloride (LiCl) at different concentrations (0, 5 mmol/L, and 10 mmol/L) and time (12 h, 16 h and 24 h). After the treatment, cells were counted, cell cycle profile was measured by BrdU labeling and flow cytometry, and expression of cyclin D1 and cyclin B1 were detected by Western blotting. The results showed that after 24h of 10mmol/L but not 5mmol/L LiCl treatment, proliferation of cells was slowed down as manifested by delayed confluence and cell number accumulation (P<0.05). Lithium did not change the percentage of cells in S phase (P>0.05), but 24 h incubation with 10 mmol/L LiCl induced a G2/M cell cycle arrest. Furthermore, 10mmol/L LiCl elevated cyclin D1 expression after 12h treatment, while expression of cyclin B1 increased more significantly after 24h incubation. These data demonstrate that lithium inhibits proliferation of pig airway epithelial cells by inhibiting cell cycle progression, and suggest that lithium-sensitive molecule(s) such as glycogen synthase kinase 3 may have a role in the regulation of growth of airway epithelial cells.
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References
Phiel C J and Klein P S. Molecular targets of lithium action. Annu Rev Pharmacol Toxicol, 2001, 41: 789
Ohtekei T, Parsons M, Zakarian Aet al. Negative regulation of T cell proliferation and interleukin 2 production by the serine threonine kinase GSK-3. J Exp Med, 2000, 192: 99
Smith E, Coetzee G A, and Frenkel B. Glucocorticoids inhibit cell cycle progression in differentiating osteoblasts via glycogen synthase kinase-3β. J Biol Chem, 2002, 277: 18191
Mao C D, Hoang P, DiCorleto P E. Lithium inhibits cell cycle progression and induces stabilization of p53 in bovine aortic endothelial cells. J Biol Chem, 2001, 276: 26180
Rössig L, Badorff C, Holzmann Yet al. Glycogen synthase kinase-3 couples AKT-dependent signaling to the regulation of p21Cipl degradation. J Biol Chem, 2002, 277: 9684
Smits V A J, Essers M A G, Loomans D A Eet al. Inhibition of cell proliferation by lithium is associated with interference in cdc2 activation. FEBS Letters, 1999: 457: 23
Chen F, Wu R, Wang Xet al. Effects of cigarette smoke extract on the expression of β-catenin and tyrosine phosphorylation in airway epithelial cell (Chinese). Chin J Med, 2001, 81: 406
Jope R S. Lithium and GSK-3: one inhibitor, two inhibitory actions, multiple outcomes. Trends Pharmacol Sci, 2003, 24: 441
Doble B W and Woodgett J R. GSK-3: tricks of the trade for a multi-tasking kinase. J Cell Sci, 2003, 116: 1175
Qu L, Huang S, Baltzis Det al. Endoplasmic reticulum stress induces p53 cytoplasmic localization and prevents p53-dependent apoptosis by a pathway involving glycogen synthase kinase-3. Genes Dev, 2004, 18: 261
Hamelers I H L, van Schaik R F M A, Sipkema Jet al. Insulin-like growth factor I triggers nuclear accumulation of cyclin D1 in MCF-7S breast cancer cells. J Biol Chem, 2002, 277: 47645 (Continued from page 313)
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CHEN Wenshu, male, born in 1968, M. D., Ph. D.
This project was supported by a grant from National Natural Science Foundation of China (No. 30200115).
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Wenshu, C., Renliang, W., Xi, W. et al. Effect of lithium on cell cycle progression of pig airway epithelial cells. Current Medical Science 24, 318–321 (2004). https://doi.org/10.1007/BF02861857
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DOI: https://doi.org/10.1007/BF02861857