Transient Glutathione Depletion Determines Terminal Differentiation in HL-60 CellsReport as inadecuate




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Oxidative Medicine and Cellular Longevity - Volume 3 2010, Issue 1, Pages 53-60



Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY, USA

Department of Radiation Oncology, University of Rochester School of Medicine, Rochester, NY, USA

Department of Pediatrics, University of Rochester School of Medicine, Rochester, NY, USA

Received 6 October 2009; Revised 21 October 2009; Accepted 21 October 2009

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.

Abstract

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.





Author: Suzanne M. Krance, Peter C. Keng, James Palis, and Nazzareno Ballatori

Source: https://www.hindawi.com/



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