Enzyme-catalysed conjugations of glutathione with unsaturated compounds

Boyland, E.; Chasseaud, L. F.

doi:10.1042/bj1040095

Cited by 308 publications

(134 citation statements)

References 17 publications

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“…Diethylmaleate (DEM) is an indirect oxidant that yields an accumulation of endogenously produced ROS through a GSH depletion (20 and DEM induce ERKs activation. Cell lysates containing 25 g of proteins were resolved by electrophoresis on a 10% SDS-PAGE, transferred to a nitrocellulose membrane, and subjected to immunoblot analysis with antibodies specific for phospho-ERKs.…”

Section: Effects Of Redox Changes Mediated By Dem and H 2 O 2 -mentioning

confidence: 99%

“…We previously developed a procedure to induce redox modification in intact cells (19): this is based on the exposure of cells to diethylmaleate (DEM), a GSH depleting agent (20). This experimental system allows the alteration of the concentrations of endogenously generated ROS by inactivating the scavenging systems based on GSH, through the formation of GSH-DEM conjugates.…”

mentioning

confidence: 99%

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Protein Kinase B Activation by Reactive Oxygen Species Is Independent of Tyrosine Kinase Receptor Phosphorylation and Requires Src Activity

Esposito¹,

Chirico²,

Gesualdi³

et al. 2003

Journal of Biological Chemistry

111

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Section: Effects Of Redox Changes Mediated By Dem and H 2 O 2 -mentioning

confidence: 99%

mentioning

confidence: 99%

Protein Kinase B Activation by Reactive Oxygen Species Is Independent of Tyrosine Kinase Receptor Phosphorylation and Requires Src Activity

Esposito¹,

Chirico²,

Gesualdi³

et al. 2003

Journal of Biological Chemistry

111

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“…That GSH might be involved in the lectin-activated proliferation of T lymphocytes (T cells) was suggested by studies in which human peripheral blood lymphocytes were found to exhibit decreased proliferation after treatment with diamide (5) and with 2-cyclohexene-1-one (6). Diamide decreases GSH levels by oxidizing GSH (7), and compounds such as 2-cyclohexene-1-one react with GSH to form conjugates (8); however, these compounds act nonspecifically and thus may be expected to have effects other than depletion of GSH. Studies in this laboratory (4,9) and subsequently in others (10)(11)(12)(13) in which peripheral blood mononuclear cells were treated with L-buthionine-(S,R)-sulfoximine (BSO) (14)(15)(16), which selectively inhibits y-glutamylcysteine synthetase and thus GSH synthesis, gave much stronger support to the view that GSH is required for proliferation.…”

mentioning

confidence: 99%

Glutathione regulates activation-dependent DNA synthesis in highly purified normal human T lymphocytes stimulated via the CD2 and CD3 antigens.

Suthanthiran

Anderson

Sharma

et al. 1990

Proc. Natl. Acad. Sci. U.S.A.

335

176

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Regulation of proliferation of normal human T lymphocytes (T cells) by glutathione (GSH) was explored with T-cell activation models that-do not require accessory cell signals. L-Buthionine-(S,R)-sulfoximine (BSO), which inactivates y-glutamylcysteine synthetase and therefore inhibits GSH synthesis, inhibited proliferation elicited by monoclonal antibodies directed at cluster designation 2 (CD2) and CD3

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“…27) In addition, enzyme-catalyzed alkylation of the thiol group of cystein with a,b-unsaturated carbonyl compounds has been observed. 28) The antimicrobial activity of a,b-unsaturated ketones is due to their reactions with essential thiol groups in bacteria and fungi, resulting in b-ketothioethers. 29) Electron densities on b-carbons are lower 30) than on a-carbons in various unsaturated ketones, and thus the attack of the nucleophils should occur at the b-carbon atoms.…”

mentioning

confidence: 99%

Cytotoxicity of Some Azines of Acetophenone Derived Mono-Mannich Bases against Jurkat Cells

Gül

Vepsäläinen

et al. 2003

Biological & Pharmaceutical Bulletin

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Mannich bases have several biological activities such as antimicrobial, [1][2][3][4][5] cytotoxic, [6][7][8][9] anticancer, 10) analgesic, 11) anti-inflammatory, 12,13) diuretic 14,15) and anticonvulsant [16][17][18][19] activities. An amino ketone, Mannich base, containing at least one activated hydrogen atom at the b position to an amino function, can undergo deamination in vivo 20) or under simulated in vitro conditions 1,3,6) to liberate the corressponding a,b-unsaturated ketones. The a,b-unsaturated ketone is an active center for nucleophilic attack. The biological activities of Mannich bases, such as antimicrobial, [1][2][3]21,22) cytotoxic and anticancer 6,9,23) activities, have been attributed to these liberated a,b-unsaturated ketones which can alkylate nucleophiles, especially thiol groups 1,6,24,25) rather than amino and hydroxyl groups, 26) by Michael type addition reactions of nucleophiles to a,b-unsaturated ketones.27) In addition, enzyme-catalyzed alkylation of the thiol group of cystein with a,b-unsaturated carbonyl compounds has been observed. 28)The antimicrobial activity of a,b-unsaturated ketones is due to their reactions with essential thiol groups in bacteria and fungi, resulting in b-ketothioethers.29) Electron densities on b-carbons are lower 30) than on a-carbons in various unsaturated ketones, and thus the attack of the nucleophils should occur at the b-carbon atoms. It was also shown that increased antimicrobial activity was associated with an increased breakdown of the Mannich bases.29) Similarly, a number of a,b-unsaturated ketones have alkylating ability against biologically important nucleophiles to produce cytotoxicity. 21,23) The amino group in Mannich bases would increase the water solubilizing property of the molecule, which may assist in transportation of the compound to the site of action.Production of thiol adducts in the stability studies, 1,3,6) carried out under in vitro physiological conditions (in phosphate buffer with pH 7.4, at 37°C), with 2-mercaptoethanol, various unsaturated ketones or Mannich bases, suggests that a,bunsaturated ketones and Mannich bases producing unsaturated ketones by deamination to exert their antimicrobial activities by thiol alkylation of unsaturated ketones.Clark and co-workers 31) found that the thiol adduct had the greatest fungitoxicity, which was probably due to the same reaction. Dimmock et al. (1994) have shown that Mannich bases of conjugated styryl ketones inhibit one or more of the following enzymes in the glutathione metabolic pathway: namely, glutathione S-transferases, glutathione reductase, gamma-glutamyl transpeptidase and glutathione peroxidase in Candida albicans. 32) They concluded that the antifungal activity of the Mannich bases of conjugated styryl ketones may be due, at least in part, to interference with the GSH metabolic pathway. In one of our previous studies, we observed that mono-Mannich bases and bis Mannich bases decrease the total glutathione level in a dose-dependent manner when Jurkat cells are exposed to the co...

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Enzyme-catalysed conjugations of glutathione with unsaturated compounds

Cited by 308 publications

References 17 publications

Protein Kinase B Activation by Reactive Oxygen Species Is Independent of Tyrosine Kinase Receptor Phosphorylation and Requires Src Activity

Protein Kinase B Activation by Reactive Oxygen Species Is Independent of Tyrosine Kinase Receptor Phosphorylation and Requires Src Activity

Glutathione regulates activation-dependent DNA synthesis in highly purified normal human T lymphocytes stimulated via the CD2 and CD3 antigens.

Cytotoxicity of Some Azines of Acetophenone Derived Mono-Mannich Bases against Jurkat Cells

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