The relationship between nuclear glutathione levels and resistance to melphalan in human ovarian tumour cells

Britten, Richard A.; Green, J.A.; Broughton, Caroline; Browning, Paul; White, R.E.; Warenius, Hilmar M.

doi:10.1016/0006-2952(91)90642-i

Cited by 28 publications

(14 citation statements)

References 8 publications

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“…Based on this findings, we have designed a model to study the effects on the cell proliferation parameters caused by GSH depletion both in the nucleus and the cytoplasm, using 100µM DEM, comparing to the administration of 10 µM BSO when nuclear GSH level is preserved. As reported previously by various authors (Britten et al, 1991;Green et al, 2006;Thomas et al, 1995) nuclear GSH pool was preserved. By contrast, depletion of glutathione levels by DEM induces a marked decrease in nuclear glutathione levels.…”

Section: The Depletion Of Nuclear Glutathione Hampers the Cell Cycle supporting

confidence: 83%

The Nuclear Compartmentation of Glutathione: Effect on Cell Cycle Progression

Marković¹,

Mora²,

Gimeno³

et al. 2011

Selected Topics in DNA Repair

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Section: The Depletion Of Nuclear Glutathione Hampers the Cell Cycle supporting

confidence: 83%

The Nuclear Compartmentation of Glutathione: Effect on Cell Cycle Progression

Marković¹,

Mora²,

Gimeno³

et al. 2011

Selected Topics in DNA Repair

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“…GSH concentrations in the nucleus account for 10–15% of total cellular GSH, and 1–2% of this total cellular GSH pool residing in the nucleus may be resistant to depletion by chemical agents such as L-buthionine-[ S,R ]-sulfoximine (BSO)[45–49]. Thus, characterization of nuclear GSH concentration and function can indicate GSH utility in nuclear protection from oxidant insult, resulting in the faithful conservation of DNA replication and improved DNA repair capabilities.…”

Section: Discussionmentioning

confidence: 99%

Simultaneous quantitation of oxidized and reduced glutathione via LC-MS/MS: An insight into the redox state of hematopoietic stem cells

Carroll

Howard

Zhu

et al. 2016

Free Radical Biology and Medicine

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Cellular redox balance plays a significant role in the regulation of hematopoietic stem-progenitor cell (HSC/MPP) self-renewal and differentiation. Unregulated changes in cellular redox homeostasis are associated with the onset of most hematological disorders. However, accurate measurement of the redox state in stem cells is difficult because of the scarcity of HSC/MPPs. Glutathione (GSH) constitutes the most abundant pool of cellular antioxidants. Thus, GSH metabolism may play a critical role in hematological disease onset and progression. A major limitation to studying GSH metabolism in HSC/MPPs has been the inability to measure quantitatively GSH concentrations in small numbers of HSC/MPPs. Current methods used to measure GSH levels not only rely on large numbers of cells, but also rely on the chemical/structural modification or enzymatic recycling of GSH and therefore are likely to measure only total glutathione content accurately. Here, we describe the validation of a sensitive method used for the direct and simultaneous quantitation of both oxidized and reduced GSH via liquid chromatography followed by tandem mass spectrometry (LC-MS/MS) in HSC/MPPs isolated from bone marrow. The lower limit of quantitation (LLOQ) was determined to be 5.0 ng/mL for GSH and 1.0 ng/mL for GSSG with lower limits of detection at 0.5 ng/mL for both glutathione species. Standard addition analysis utilizing mouse bone marrow shows that this method is both sensitive and accurate with reproducible analyte recovery. This method combines a simple extraction with a platform for the high-throughput analysis, allows for efficient determination of GSH/GSSG concentrations within the HSC/MPP populations in mouse, chemotherapeutic treatment conditions within cell culture, and human normal/leukemia patient samples. The data implicate the importance of the modulation of GSH/GSSG redox couple in stem cells related diseases.

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“…In conclusion, the importance of nuclear GSH compartmentation for the onset of proliferation in cells has been demonstrated (Borrás et al, 2004;Markovic et al, 2007) and the levels of nuclear GSH have been associated with increased resistance to radiation and xenobiotics (Britten et al, 1991;Biaglow et al, 1983;Smith et al, 1996;Morales et al, 1998;Hansen et al, 2002). It appears that the study of cellular compartmentalization of GSH in different phases of cell cycle may be advantageous to understand better cell physiology and the metabolic changes involved in a series of vital cell processes.…”

Section: Changes In the Nuclear Distribution Of Glutathione During Cementioning

confidence: 94%

“…Indeed, in 1998, Voehringer andcolleagues (Voehringer et al, 1998) showed that over-expression of Bcl-2 recruits GSH to the nucleus preventing apoptosis; other authors have reported that over-expression of Bcl-2 leads to higher cellular levels of GSH (Ellerby et al, 1996;Meredith et al, 1998;Rimpler et al, 1999;Schor et al, 2000;Vahrmeijer et al, 2000;Hoetelmans et al, 2003). Furthermore, it has been reported that depleting the nuclear pool of GSH by oxidative stress potentiates the cytotoxic effects of the DNA-alkylating agent melphalan in cultured human melanoma cells (Britten et al, 1991). Therefore, GSH may be protecting cells against apoptosis using a mitochondrial and nuclear mechanism.…”

Section: High Glutathione Levels Increase Cellular Resistance To Apopmentioning

confidence: 99%