Transient Glutathione Depletion Determines Terminal Differentiation in HL-60 Cells. Issue 1 (2010)

• Record Type: Journal Article
• Authors: Krance, Suzanne M.; Keng, Peter C.; Palis, James; Ballatori, Nazzareno
• Is Part Of: Oxidative medicine and cellular longevity. Volume 3:Issue 1(2010)
• Page Start: 53
• Page End: 60
• Publication Date: 2010
• Subjects: glutathione -- cell differentiation -- thiol levels -- vitamin D3 -- all-trans retinoic acid -- NADPH oxidase -- N-acetylcysteine; Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.4161/oxim.3.1.10405
• Languages: English
• ISSNs: 1942-0900

Abstract

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.