Effect of extracellular magnesium on Topoisomerase II activity and expression in human leukemia HL-60 cells

Topoisomerase II (TopoII) is a Mg‐dependent enzyme involved in topological modifications of DNA that are crucial to the regulation of cell proliferation and possibly differentiation. To investigate the role of Mg availability in the modulation of TopoII in whole cells, we studied enzyme activity and...

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Published inJournal of cellular biochemistry Vol. 78; no. 2; pp. 325 - 333
Main Authors Covacci, Valeria, Bruzzese, Nicodemo, Sgambato, Alessandro, Ganapathi, Ram, Cittadini, Achille, Wolf, Federica I.
Format Journal Article
LanguageEnglish
Published New York John Wiley & Sons, Inc 01.08.2000
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Summary:Topoisomerase II (TopoII) is a Mg‐dependent enzyme involved in topological modifications of DNA that are crucial to the regulation of cell proliferation and possibly differentiation. To investigate the role of Mg availability in the modulation of TopoII in whole cells, we studied enzyme activity and expression in HL‐60 cells grown in the presence of decreasing amounts of extracellular Mg (0.5, 0.03, and 0.01 mM MgSO4). In comparison to cells grown in 0.5 mM Mg, cells grown in 0.03 mM Mg exhibited a decrease in TopoII activity, as evidenced by reduced induction of DNA/TopoII cleavable complexes and apoptosis by etoposide and teniposide. Enzyme activity was restored by the readdition of Mg (0.5 and 1.5 mM) in the incubation medium, confirming that this effect was indeed modulated by extracellular Mg. Restriction of Mg to 0.01 mM was associated with a dramatic decrease in TopoII activity resembling that observed in HL‐60 cells differentiated by dimethyl sulfoxide treatment. The restriction of Mg, while decreasing enzyme activity, was found to upregulate TopoII protein expression, determined by Western blot analysis. The increase of TopoII protein levels was correlative with the degree of Mg deprivation. Collectively, these results indicate that extracellular levels of Mg may control availability of intracellular Mg, thus affecting the regulation of TopoII activity/expression and downstream processes of cell proliferation and/or differentiation. J. Cell. Biochem. 78:325–333, 2000. © 2000 Wiley‐Liss, Inc.
Bibliography:ArticleID:JCB14
MURST - No. 40% N 9706247467
istex:31187C85827EF5E8846C492C18701DA59057CE24
Department of Health and Human Services, U.S. Public Health Service, U.S. Public Health Service - No. CA35531; No. CA74939
ark:/67375/WNG-82SZKP1R-X
The first two authors equally contributed to the work.
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ISSN:0730-2312
1097-4644
DOI:10.1002/(SICI)1097-4644(20000801)78:2<325::AID-JCB14>3.0.CO;2-K