Magnesium Deficiency Affects Mammary Epithelial Cell Proliferation: Involvement of Oxidative Stress

Abstract

Low Mg availability reversibly inhibited the growth of mammary epithelial HC11 cells by increasing the number of cells in the G0/G1 phase of the cell cycle. Because low Mg has been reported to promote oxidative reactions, we considered that low Mg-dependent growth arrest was mediated by oxidative stress. Surprisingly, both dichlorofluorescein-detectable reactive oxygen species and hydrogen peroxide-induced oxidative DNA damage were found to be lower in cells cultured in low Mg than in cells grown under control or high-Mg conditions. Gene expression profiling of low- and high-Mg cells showed the modulation of several genes, some regulating cell proliferation. In addition, low Mg cells also displayed overexpression of glutathione S-transferase (GST), leading to increased enzymatic activity. Of note, GST has been shown to modulate cell growth; therefore, we suggest that in low-Mg cells, GST upregulation might have a dual role in protecting against oxidative stress and in modulating cell proliferation.

ACKNOWLEDGMENTS

Work supported by Collaborative Linkage NATO grant to A. Mazur, J. A. M. Maier, and F. I. Wolf (2002–2004); MIUR 60%, and linea D1 2004–2007 to F. I. Wolf.

Notes

^a Abbreviations are as follows: H, high magnesium (Mg); L, low Mg; Crk, CT10 sarcoma oncogene cellular homolog; Ets, E26 avian erythroblastosis virus transformation specific protein; GADD, growth arrest and DNA damage inducible protein; HSP, heat shock protein; TGF, transforming growth factor; ↓ down-expression (each ↓ corresponds to 50% decrease vs. control HC11 cells), ↑ over-expression (each ↑ corresponds to twofold increase vs. control HCl1 cells).

^a Abbreviations are as follows: GST, glutathione S-transferase; Mg, magnesium; L, low Mg; Data are mean ± SEM (number of experiments). The data groups with different letters are statistically different (Tukey's multiple comparison test).