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• W2897394286 abstract "The Allium vegetable-derived metabolite, S-alk(en)ylmercaptocysteine (CySSR), has been reported to modulate oxidative stress and inflammatory responses. However, the underlying mechanisms of action and structure-activity relationships are not completely understood. We investigated the mechanistic basis of the protective effects of CySSR on pro-inflammatory responses involving redox/oxidative stress induced by E. coli lipopolysaccharide (LPS) using RAW 264.7 cells. CySSR (R = allyl, A or 1-propenyl, Pe) pre-treatments conferred concentration-dependent reductions in cytokines (TNF-α, IL-1β and IL-6), NO production and iNOS (inducible nitric synthase) overexpression, and attenuated oxidant production in LPS-stimulated RAW 264.7 cells where viability remained > 90%. These protective effects were manifested through inhibited activation of the nuclear factor-kappa B (NF-κB) signaling pathway via suppression of the IκB kinases (IKK) phosphorylation possibly by transforming growth factor β-activated kinase 1 or a kinase further upstream the canonical NF-κB signaling pathway. The attenuation of LPS-induced inflammation by CySSRs was associated with enhanced levels of cellular cysteine (CySH) and glutathione (GSH) mediated by cellular import/reduction of CySSR and the induction of glutamate cysteine ligase (GCL), one of > 200 nuclear factor erythroid 2-related factor 2 (Nrf2) regulated proteins. The reduction of anti-inflammatory effect of CySSR following pretreatment of cells with L-buthionine-S,R-sulfoximine (BSO) implicates GSH having a major role in reducing inflammation, likely in the context of other Nrf2-regulated antioxidant enzymes that scavenge H2O2 and peroxides using GSH as co-substrate. The anti-inflammatory effect of CySSPe was significantly greater than CySSA for almost all indicators measured, and cell metabolites of CySSRs may have a role in attenuating NF-κB signaling." @default.
• W2897394286 created "2018-10-26" @default.
• W2897394286 creator A5026978295 @default.
• W2897394286 creator A5041159870 @default.
• W2897394286 date "2018-12-01" @default.
• W2897394286 modified "2023-10-16" @default.
• W2897394286 title "S-Alk(en)ylmercaptocysteine suppresses LPS-induced pro-inflammatory responses in murine macrophages through inhibition of NF-κB pathway and modulation of thiol redox status" @default.
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• W2897394286 doi "https://doi.org/10.1016/j.freeradbiomed.2018.10.424" @default.
• W2897394286 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30342185" @default.
• W2897394286 hasPublicationYear "2018" @default.
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