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• W1763772253 endingPage "1844" @default.
• W1763772253 startingPage "1835" @default.
• W1763772253 abstract "Abstract In endothelial cells, the intracellular level of glutathione is depleted during offering protection against proinflammatory cytokine TNF-α-induced oxidative stress. Administration of anti-inflammatory drugs, i.e., N-acetylcysteine (NAC) or mitoquinone-Q (mito-Q) in low concentrations in the human pulmonary aortic endothelial cells offered protection against depletion of reduced glutathione and oxidative stress mediated by TNF-α. However, this study addressed that administration of NAC or mito-Q in high concentrations resulted in a biphasic response by initiating an enhanced generation of both reduced glutathione and oxidized glutathione and enhanced production of reactive oxygen species, along with carbonylation and glutathionylation of the cellular proteins. This study further addressed that IκB kinase (IKK), a phosphorylation-dependent regulator of NF-κB, plays an important regulatory role in the TNF-α-mediated induction of the inflammatory cell surface molecule ICAM-1. Of the two catalytic subunits of IKK (IKKα and IKKβ), low concentrations of NAC and mito-Q activated IKKα activity, thereby inhibiting the downstream NF-κB and ICAM-1 induction by TNF-α. High concentrations of NAC and mito-Q instead caused glutathionylation of IKKα, thereby inhibiting its activity that in turn enhanced the downstream NF-κB activation and ICAM-1 expression by TNF-α. Thus, establishing IKKα as an anti-inflammatory molecule in endothelial cells is another focus of this study. This is the first report that describes a stressful situation in the endothelial cells created by excess of antioxidative and anti-inflammatory agents NAC and mito-Q, resulting in the generation of reactive oxygen species, carbonylation and glutathionylation of cellular proteins, inhibition of IKKα activity, and up-regulation of ICAM-1expression." @default.
• W1763772253 created "2016-06-24" @default.
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• W1763772253 creator A5036894204 @default.
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• W1763772253 date "2007-02-01" @default.
• W1763772253 modified "2023-10-18" @default.
• W1763772253 title "High Concentration of Antioxidants <i>N</i>-Acetylcysteine and Mitoquinone-Q Induces Intercellular Adhesion Molecule 1 and Oxidative Stress by Increasing Intracellular Glutathione" @default.
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• W1763772253 doi "https://doi.org/10.4049/jimmunol.178.3.1835" @default.
• W1763772253 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/17237434" @default.
• W1763772253 hasPublicationYear "2007" @default.
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