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- W2012120545 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., <i>N</i>-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.
- W2012120545 created "2016-06-24" @default.
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- W2012120545 date "1996-10-01" @default.
- W2012120545 modified "2023-09-26" @default.
- W2012120545 title "Knowledge and use of Periconceptual Folic Acid Supplements by British Forces Germany Personnel and Dependents" @default.
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- W2012120545 doi "https://doi.org/10.1136/jramc-142-03-08" @default.
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