Magnesium deficiency affects mammary epithelial cell proliferation: involvement of oxidative stress.
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.
Wolf
Federica I
FI
Istituto di Patologia Generale, e Centro di Ricerche Oncologiche Giovanni XXIII, Facoltà di Medicina, Università Cattolica del Sacro Cuore, Rome, Italy. fwolf@rm.unicatt.it
Trapani
Valentina
V
Simonacci
Matteo
M
Boninsegna
Alma
A
Mazur
Andrzej
A
Maier
Jeanette A M
JA
D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D020552:Comet Assay; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000166:cytology*; D016193:G1 Phase / Q000187:drug effects / Q000502:physiology; D020869:Gene Expression Profiling; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D008274:Magnesium / Q000494:pharmacology*; D008275:Magnesium Deficiency / Q000473:pathology* / Q000503:physiopathology; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D017382:Reactive Oxygen Species; D016192:Resting Phase, Cell Cycle / Q000187:drug effects / Q000502:physiology; D015854:Up-Regulation
D017382:Reactive Oxygen Species; D005982:Glutathione Transferase; D008274:Magnesium