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• W2040807344 startingPage "889" @default.
• W2040807344 abstract "Oxidative processes are considered to play a crucial role in the induction of cell adhesion molecules, a key event in inflammatory processes. We recently reported on an unexpected unidirectional effect of an overexpressed antioxidant [phospholipid hydroperoxide glutathione peroxidase (PHGPx)] and an oxidant [15-lipoxygenase (15-LOX)] enzyme on the basal and interleukin-1 induced vascular cell adhesion molecule-1 (VCAM-1) expression in vascular smooth muscle cells (SMC). Both enzymes inhibited VCAM-1 expression and reduced the cellular protein thiol content, thus, both exerting an oxidant effect. We now investigated whether transcription factors known to be regulated by oxidation, i.e., the nuclear factor-kappaB and the Keap1/Nrf2 system, were affected in our set of cells: SMC, SMC(PHGPx), and SMC(LOX), as well as ECV and ECV(PHGPx). PHGPx and 15-LOX inhibited nuclear factor-kappaB activation most efficiently at a step downstream of DNA binding, which explains their inhibitory effect on VCAM-1 expression. Both enzymes up-regulated endogenous heme oxygenase-1 most probably via activation of Nrf2. Transfected Nrf2 strongly inhibited VCAM-1 promoter activity, which could be reversed by cotransfection with Keap1. The key player in this complex cross-talk obviously is heme oxygenase-1, which is known to be induced by oxidant-activated Nrf2. The moderate oxidative stress initiated by enhanced PHGPx or 15-LOX activity appears to induce a defense system that diminishes the response to further proinflammatory stimuli." @default.
• W2040807344 created "2016-06-24" @default.
• W2040807344 creator A5026212298 @default.
• W2040807344 creator A5037485994 @default.
• W2040807344 date "2005-07-01" @default.
• W2040807344 modified "2023-10-14" @default.
• W2040807344 title "NF-κB, Nrf2, and HO-1 Interplay in Redox-Regulated VCAM-1 Expression" @default.
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• W2040807344 doi "https://doi.org/10.1089/ars.2005.7.889" @default.
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