Magnesium restriction induces granulocytic differentiation and expression of p27(KIP1) in human leukemic HL-60 cells

Valeria Covacci, Nicodemo Bruzzese, Alessandro Sgambato, Arianna Di Francesco, Matteo A. Russo, Federica I. Wolf, Achille Cittadini

Research output: Contribution to journalArticlepeer-review


When cultured in Mg restricted medium, human leukemic HL-60 cells develop morphological and functional granulocytic differentiation. In 0.03 mM Mg, cells display the distinctive features of differentiation, without appreciable inhibition of proliferation. In 0.01 mM Mg, cells show terminal differentiation, accompanied by clear inhibition of proliferation. Such cells accumulate in the G0/G1 phase and subsequently die via apoptosis, similar to HL-60 cells that have been induced to differentiate by DMSO. These phenotypic changes are associated with a marked increase in the expression level of the cyclin dependent kinase inhibitor p27(Kip1). Cyclin E expression is also slightly increased in Mg restricted cells, whereas no changes are observed in the expression level of cyclin D1. We also show that during differentiation cell total Mg decreases, whereas [Mg2+](i) increases in both Mg-depleted and DMSO-treated cells. These data suggest that the maturation process is paralleled by a redistribution of intracellular Mg, leading to a shift from the bound to the free form. These changes could modulate the kinetics of Mg- dependent enzyme(s) that are involved in the control of the differentiation pathway. We propose that this mode may represent an useful tool for the study of the mechanisms of cell differentiation and related events, such as aging and death.

Original languageEnglish
Pages (from-to)313-322
Number of pages10
JournalJournal of Cellular Biochemistry
Issue number3
Publication statusPublished - Sep 1 1998


  • Apoptosis
  • CD11b
  • Cell cycle
  • Cell magnesium
  • Cyclins
  • HL-60 cells
  • Myeloid differentiation
  • p27(Kip1)
  • Proliferation

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology


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