Involvement and relative importance of at least two distinct mechanisms in the effects of 2‐mercaptoethanol on murine lymphocytes in culture

Pruett, Stephen B.; Obiri, Nicholas I.; Kiel, Johnathan L.

doi:10.1002/jcp.1041410107

Cited by 27 publications

(8 citation statements)

References 17 publications

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“…Further melatonin, NAC, and DTT individually or in combination with cysteine did not enhance development [ 43 ] suggesting that a reduction in ROS like an increase in synthesis of GSH can be uncoupled from development. These results are in line with the estimate that only 25–45% of 2ME’s benefits for lymphoid functions in vitro are due to antioxidant activity alone [ 87 ].…”

Section: Possible Thiol Mechanismssupporting

confidence: 90%

A review: alteration of in vitro reproduction processes by thiols —Emphasis on 2-mercaptoethanol

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2014

Journal of Reproduction and Development

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Descriptions of organosulfurs altering biologically relevant cellular functions began some 40 years ago when murine in vitro cell mediated and humoral immune responses were shown to be dramatically enhanced by any of four xenobiotic, sulfhydryl compounds—2-mercaptoethanol (2ME), dithiothreitol (DTT), glutathione, and L-cysteine; the most effective were 2ME and DTT. These findings triggered a plethora of reports defining 2ME benefits for a multitude of immunological processes. This in turn led to investigations on 2ME alterations of (a) immune functions in other species, (b) activities of other cell-types, and (c) in vivo diseases. In addition, these early findings preceded the identification of previously undefined anticarcinogenic chemicals in specific foods as organosulfurs. Taken all together, there is little doubt that organosulfur compounds have enormous benefits for cellular functions and for a multitude of diseases. Issues of importance still to be resolved are (a) clarification of mechanisms that underlie alteration of in vitro and in vivo processes and perhaps more importantly, (b) which if any in vitro alterations are relevant for (i) alteration of in vivo diseases and (ii) identification of other diseases that might therapeutically benefit from organosulfurs. As one means to address these questions, reviews of different processes impacted by thiols could be informative. Therefore, the present review on alterations of in vitro fertilization processes by thiols (mainly 2ME, since cysteamine alterations have been reviewed) was undertaken. Alterations found to occur in medium supplemented with 2ME were enhancement, no effect, or inhibition. Parameters associated with which are discussed as they relate to postulated thiol mechanisms.

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Section: Possible Thiol Mechanismssupporting

confidence: 90%

A review: alteration of in vitro reproduction processes by thiols —Emphasis on 2-mercaptoethanol

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2014

Journal of Reproduction and Development

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“…The inhibition of MPOmediated CL may be due to a general antioxidant effect of low 3-AT levels (12,32) but could also reflect binding of 3-AT to the active site of MPO (14), which could be a prelimina13~ step in aminomelanin synthesis. Past reports of peroxidase-mediated melanin formation (4,6,(23)(24)(25)(26)(27)(28), coupled with the reported cytotoxicity of melanin synthesis precursors and byproducts, such as peroxides, in melanoma cells (8,10,18,31,33,36), implicate MPO catalysis of 3-AT polymerization as a means for myeloid leukemia cell destruction.…”

Section: Discussionmentioning

confidence: 99%

Selective cytotoxicity of 3-amino-l-tyrosine correlates with peroxidase activity

Bruno

Herman

Cano

et al. 1999

In Vitro Cell.Dev.Biol.-Animal

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In the presence of 3-amino-L-tyrosine (3-AT), abundant brown pigment forms in human HL-60 cells, but not in a variety of other cell lines, which are reported to be lower in mean myeloperoxidase (MPO) content than HL-60. Cells were assessed for peroxidase activity with an ABTS-based colorimetric assay and compared to values obtained with known amounts of human myeloperoxidase. HL-60 cells were estimated to contain the equivalent of 37.1 ng myeloperoxidase/10(6) cells versus 26.1 and 5.0 ng/10(6) cells for human K562 and murine RAW 264.7 cell lines, respectively. HL-60 cells exhibited a nearly 60% inhibition of proliferation and > 70% reduction in cell viability after 4 d of culture in the presence of 100 microg 3-AT per ml. Higher concentrations of 3-AT (up to 400 microg/ml) for 4 d reduced HL-60 proliferation by 80% and decreased viability to 1-3%. Comparable levels of cytotoxicity were achieved in KG-1 cells after 7 d with 200 or 400 microg 3-AT per ml. K562 cells exhibited a 40% reduction in cell number after 7 d with 400 microg 3-AT per ml, but concentrations less than 400 microg/ml did not significantly affect K562 proliferation. K562 viability remained unchanged with doses of 3-AT up to 400 microg/ml. RAW 264.7 cells exhibited unchanged viability and proliferation in the presence of 3-AT at concentrations up to 400 microg 3-AT per ml. K562, KG-1, and RAW 264.7 cells exhibited no evidence of brown pigment formation in the presence of 3-AT and medium containing 10% fetal bovine serum. However, RAW 264.7 cells that were converted to protein-free medium and exposed to 3-AT exhibited intense brown pigment in some cell nuclei. A high percentage of HL-60 cells treated with 3-AT exhibited membrane blebbing, pyknosis, and nuclear fragmentation, which was not observed among other 3-AT-treated cell lines. A mechanism involving toxic intermediates of peroxidase-mediated "aminomelanin" formation is hypothesized.

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“…The requirement for a reducing extracellular microenvironment for T cell activation and proliferation has been suspected from their dependence on an exogenous reductant, such as b-mercaptoethanol, added to the culture medium (20). The basis of this dependence has been ascribed to the inability of naïve T cells to efficiently transport cystine, the oxidized form of the amino acid that is relatively abundant in circulation.…”

Section: Discussionmentioning

confidence: 99%

Differential Dependence on Cysteine from TranssulfurationversusTransport During T Cell Activation

Garg

Yan

Vitvitsky

et al. 2011

Antioxidants & Redox Signaling

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The synthesis of glutathione, a major cellular antioxidant with a critical role in T cell proliferation, is limited by cysteine. In this study, we evaluated the contributions of the x C -cystine transporter and the transsulfuration pathway to cysteine provision for glutathione synthesis and antioxidant defense in naïve versus activated T cells and in the immortalized T lymphocyte cell line, Jurkat. We show that the x C -transporter, although absent in naïve T cells, is induced after activation, releasing T cells from their cysteine dependence on antigen-presenting cells. We also demonstrate the existence of an intact transsulfuration pathway in naïve and activated T cells and in Jurkat cells. The flux through the transsulfuration pathway increases in primary but not in transformed T cells in response to oxidative challenge by peroxide. Inhibition of the transsulfuration pathway in both primary and transformed T cells decreases cell viability under oxidative-stress conditions. Antioxid. Redox Signal. 15, 39-47.

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Involvement and relative importance of at least two distinct mechanisms in the effects of 2‐mercaptoethanol on murine lymphocytes in culture

Cited by 27 publications

References 17 publications

A review: alteration of in vitro reproduction processes by thiols —Emphasis on 2-mercaptoethanol

A review: alteration of in vitro reproduction processes by thiols —Emphasis on 2-mercaptoethanol

Selective cytotoxicity of 3-amino-l-tyrosine correlates with peroxidase activity

Differential Dependence on Cysteine from TranssulfurationversusTransport During T Cell Activation

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