Oxidative Medicine and Cellular Longevity

Oxidative Medicine and Cellular Longevity / 2010 / Article

Open Access

Volume 3 |Article ID 764730 | https://doi.org/10.4161/oxim.3.1.10405

Suzanne M. Krance, Peter C. Keng, James Palis, Nazzareno Ballatori, "Transient Glutathione Depletion Determines Terminal Differentiation in HL-60 Cells", Oxidative Medicine and Cellular Longevity, vol. 3, Article ID 764730, 8 pages, 2010. https://doi.org/10.4161/oxim.3.1.10405

Transient Glutathione Depletion Determines Terminal Differentiation in HL-60 Cells

Received06 Oct 2009
Revised21 Oct 2009
Accepted21 Oct 2009


To better define the role of glutathione (GSH) in cell differentiation, the present study measured GSH concentrations during terminal HL-60 cell differentiation, in the presence and absence of differentiation-inducing agents, and in the presence and absence of GSH altering agents. Interestingly, there was a small transient increase in intracellular GSH levels during dimethyl sulfoxide (DMSO) or 1α,25-dihydroxyvitamin D3 (VD3) induced differentiation. This increase coincided with an increase in nitroblue tetrazolium (NBT) reduction capacity, a measure of superoxide anion production, but there was no apparent change in the GSH/glutathione disulfide (GSSG) ratio. Surprisingly, treatment of cells with low doses of 1-chloro-2,4-dinitrobenzene (CDNB; 5 µM) or diethylmaleate (DEM; 0.5 mM), which transiently deplete GSH levels to about 40% of control levels, resulted in enhanced differentiation of HL-60 cells exposed to VD3 or all-trans-retinoic acid (ATRA), as well as under un-induced conditions (i.e., spontaneous differentiation). Enhanced differentiation occurred when cells were treated with the GSH-depleting agents 4 hours after treatment with differentiation inducers. These findings indicate that intracellular GSH levels are regulated in a complex fashion during HL-60 cell differentiation, and that transient GSH depletion using low doses of CDNB and DEM enhances the differentiation process.

Copyright © 2010 Hindawi Publishing Corporation. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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