• Inicio
  • Resultados de la búsqueda
  • Adenanthin, a new inhibitor of thiol-dependent antioxidant enzymes, impairs the effector functions of human natural killer cells.

Adenanthin, a new inhibitor of thiol-dependent antioxidant enzymes, impairs the effector functions of human natural killer cells.

Immunology (2015-06-23)
Marta Siernicka, Magdalena Winiarska, Malgorzata Bajor, Malgorzata Firczuk, Angelika Muchowicz, Malgorzata Bobrowicz, Cyril Fauriat, Jakub Golab, Daniel Olive, Radoslaw Zagozdzon
RESUMEN

Natural killer (NK) cells are considered critical components of the innate and adaptive immune responses. Deficiencies in NK cell activity are common, such as those that occur in cancer patients, and they can be responsible for dysfunctional immune surveillance. Persistent oxidative stress is intrinsic to many malignant tumours, and numerous studies have focused on the effects of reactive oxygen species on the anti-tumour activity of NK cells. Indeed, investigations in animal models have suggested that one of the most important thiol-dependent antioxidant enzymes, peroxiredoxin 1 (PRDX1), is essential for NK cell function. In this work, our analysis of the transcriptomic expression pattern of antioxidant enzymes in human NK cells has identified PRDX1 as the most prominently induced transcript out of the 18 transcripts evaluated in activated NK cells. The change in PRDX1 expression was followed by increased expression of two other enzymes from the PRDX-related antioxidant chain: thioredoxin and thioredoxin reductase. To study the role of thiol-dependent antioxidants in more detail, we applied a novel compound, adenanthin, to induce an abrupt dysfunction of the PRDX-related antioxidant chain in NK cells. In human primary NK cells, we observed profound alterations in spontaneous and antibody-dependent NK cell cytotoxicity against cancer cells, impaired degranulation, and a decreased expression of activation markers under these conditions. Collectively, our study pinpoints the unique role for the antioxidant activity of the PRDX-related enzymatic chain in human NK cell functions. Further understanding this phenomenon will prospectively lead to fine-tuning of the novel NK-targeted therapeutic approaches to human disease.

MATERIALES
Referencia del producto
Marca
Descripción del producto

Sigma-Aldrich
Hydrogen peroxide solution, 30 % (w/w) in H2O, contains stabilizer
Sigma-Aldrich
L-Glutathione reduced, ≥98.0%
Sigma-Aldrich
Propidium iodide, ≥94.0% (HPLC)
Sigma-Aldrich
L-Cysteine, 97%
Sigma-Aldrich
L-Glutamine, meets USP testing specifications, suitable for cell culture, 99.0-101.0%, from non-animal source
Sigma-Aldrich
L-Cysteine, from non-animal source, BioReagent, suitable for cell culture, ≥98%
Sigma-Aldrich
N-Ethylmaleimide, crystalline, ≥98% (HPLC)
Sigma-Aldrich
L-Glutathione oxidized, ≥98% (HPLC)
Sigma-Aldrich
Propidium iodide solution, solution (1.0 mg/ml in water)
Sigma-Aldrich
L-Glutamine, ReagentPlus®, ≥99% (HPLC)
SAFC
L-Cysteine
Sigma-Aldrich
L-Glutathione reduced, suitable for cell culture, BioReagent, ≥98.0%, powder
SAFC
L-Glutamine
Sigma-Aldrich
L-Cysteine, BioUltra, ≥98.5% (RT)
Sigma-Aldrich
Hydrogen peroxide solution, 34.5-36.5%
Sigma-Aldrich
L-Glutathione reduced, BioXtra, ≥98.0%
Sigma-Aldrich
N-Ethylmaleimide, BioUltra, ≥99.0% (HPLC)
Sigma-Aldrich
Interleukin-2 human, IL-2, recombinant, expressed in E. coli, lyophilized powder, suitable for cell culture
Sigma-Aldrich
5(6)-Carboxyfluorescein diacetate N-succinimidyl ester, BioReagent, suitable for fluorescence, ≥90% (HPLC)
Sigma-Aldrich
L-Cysteine, ≥97%, FG
Sigma-Aldrich
IL-2 human, Animal-component free, recombinant, expressed in E. coli, ≥98% (SDS-PAGE), ≥98% (HPLC), suitable for cell culture
Sigma-Aldrich
L-Glutamine, BioUltra, ≥99.5% (NT)
Sigma-Aldrich
L-Glutathione oxidized, BioXtra, ≥98%
Sigma-Aldrich
L-Glutathione oxidized, ≥98%, lyophilized powder
Sigma-Aldrich
L-Glutamine, γ-irradiated, BioXtra, suitable for cell culture
Sigma-Aldrich
L-Glutathione oxidized disodium salt, ≥98%, powder
Sigma-Aldrich
N-Ethylmaleimide, BioXtra, ≥98% (HPLC)
Sigma-Aldrich
L-Cysteine, produced by Wacker Chemie AG, Burghausen, Germany, ≥98.0%
Sigma-Aldrich
Interleukin-2 human, recombinant, expressed in Pichia pastoris, suitable for cell culture
Sigma-Aldrich
Interleukin-2 from mouse, IL-2, recombinant, expressed in E. coli, lyophilized powder, suitable for cell culture