Magnesium deficiency suppresses cell cycle progression mediated by increase in transcriptional activity of p21Cip1 and p27Kip1 in renal epithelial NRK-52E cells
✍ Scribed by Akira Ikari; Hayato Sawada; Ayumi Sanada; Chie Tonegawa; Yasuhiro Yamazaki; Junko Sugatani
- Publisher
- John Wiley and Sons
- Year
- 2011
- Tongue
- English
- Weight
- 485 KB
- Volume
- 112
- Category
- Article
- ISSN
- 0730-2312
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✦ Synopsis
Lack of magnesium suppresses cell growth, but the molecular mechanism is not examined in detail. We examined the effect of extracellular magnesium deficiency on cell cycle progression and the expression of cell cycle regulators in renal epithelial NRK-52E cells. In synchronized cells caused by serum-starved method, over 80% cells were distributed in G1 phase. Cell proliferation and percentage of the cells in S phase in the presence of MgCl 2 were higher than those in the absence of MgCl 2 , suggesting that magnesium is involved in the cell cycle progression from G1 to S phase. After serum addition, the expression levels of p21 Cip1 and p27 Kip1 in the absence of MgCl 2 were higher than those in the presence of MgCl 2 . The exogenous expression of p21 Cip1 or p27 Kip1 increased the percentage in G1 phase, whereas it decreased that in S phase. The mRNA levels and promoter activities of p21 Cip1 and p27 Kip1 in the absence of MgCl 2 were higher than those in the presence of MgCl 2 . The phosphorylated p53 (p-p53) level was decreased by MgCl 2 addition. Pifithrin-a, a p53 inhibitor, decreased the p-p53, p21 Cip1 and p27 Kip1 levels, and the percentage in G1 phase in the absence of MgCl 2 . Rotenone, a mitochondrial respiratory inhibitor, decreased ATP content and increased the p-p53 level in the presence of MgCl 2 . Together, lack of magnesium may increase p21 Cip1 and p27 Kip1 levels mediated by the decrease in ATP content and the activation of p53, resulting in the suppression of cell cycle progression from G1 to S phase in NRK-52E cells.