caa a22 4500 445885505 CHVBK 20180317145558.0 cr unu---uuuuu 170323e20110301xx s 000 0 eng 10.1007/s00011-010-0256-7 doi (NATIONALLICENCE)springer-10.1007/s00011-010-0256-7 Evidence that α-lipoic acid inhibits NF-κB activation independent of its antioxidant function [Elektronische Daten] [Zhekang Ying, Thomas Kampfrath, Qinghua Sun, Sampath Parthasarathy, Sanjay Rajagopalan] Objective: α-Lipoic acid (LA) exerts beneficial effects in cardiovascular diseases though its antioxidant and/or anti-inflammatory functions. It is postulated that the anti-inflammatory function of LA results from its antioxidant function. In this study we tested whether inhibition of NF-κB by LA is dependent on its antioxidant function. Methods: Human umbilical vein endothelial cells (HUVECs) were treated with tumor necrosis factor-α (TNFα) in the presence of various antioxidants, including LA, tiron, apocynin, and tempol. The activation of the nuclear factor-κB (NF-κB) signaling pathway was then analyzed. Results: LA, but not other tested antioxidants, inhibited TNFα-induced inhibitor-kappaB-α (IκBα) degradation and VCAM-1 and COX2 expression in HUVECs. Although LA activated the phosphatidylinositol-3-kinase (PI3-kinase)/Akt pathway in HUVECs, inhibition of Akt by LY294002 did not affect inhibition of TNFα-induced IκBα degradation by LA. In transient co-transfection assays of a constitutively active mutant of IκB kinase-2 (IKK2), IKK2(EE), and a NF-κB luciferase reporter construct, LA dose-dependently inhibited IKK2(EE)-induced NF-κB activation in addition to inhibiting IKK activity in in vitro assays. Consistent with the effect on luciferase expression, LA inhibited IKK2(EE)-induced cyclo-oxygenase-2 (COX2) expression, suggesting that IKK2 inhibition by LA may be a relevant mechanism that explains its anti-inflammatory effects. Conclusions: LA inhibits NF-κB activation through antioxidant-independent and probably IKK-dependent mechanisms. Springer Basel AG, 2010 Lipoic acid nationallicence Antioxidant nationallicence NF-κB nationallicence Ying Zhekang Davis Heart and Lung Research Institute, Colleges of Medicine and Public Health, The Ohio State University, Room 110, 473W 12th Avenue, 43210-1252, Columbus, OH, USA aut Kampfrath Thomas Davis Heart and Lung Research Institute, Colleges of Medicine and Public Health, The Ohio State University, Room 110, 473W 12th Avenue, 43210-1252, Columbus, OH, USA aut Sun Qinghua Davis Heart and Lung Research Institute, Colleges of Medicine and Public Health, The Ohio State University, Room 110, 473W 12th Avenue, 43210-1252, Columbus, OH, USA aut Parthasarathy Sampath Davis Heart and Lung Research Institute, Colleges of Medicine and Public Health, The Ohio State University, Room 110, 473W 12th Avenue, 43210-1252, Columbus, OH, USA aut Rajagopalan Sanjay Davis Heart and Lung Research Institute, Colleges of Medicine and Public Health, The Ohio State University, Room 110, 473W 12th Avenue, 43210-1252, Columbus, OH, USA aut Inflammation Research SP Birkhäuser Verlag Basel 60/3(2011-03-01), 219-225 1023-3830 60:3<219 2011 60 11 https://doi.org/10.1007/s00011-010-0256-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00011-010-0256-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ying Zhekang Davis Heart and Lung Research Institute, Colleges of Medicine and Public Health, The Ohio State University, Room 110, 473W 12th Avenue, 43210-1252, Columbus, OH, USA aut NATIONALLICENCE 700 1- Kampfrath Thomas Davis Heart and Lung Research Institute, Colleges of Medicine and Public Health, The Ohio State University, Room 110, 473W 12th Avenue, 43210-1252, Columbus, OH, USA aut NATIONALLICENCE 700 1- Sun Qinghua Davis Heart and Lung Research Institute, Colleges of Medicine and Public Health, The Ohio State University, Room 110, 473W 12th Avenue, 43210-1252, Columbus, OH, USA aut NATIONALLICENCE 700 1- Parthasarathy Sampath Davis Heart and Lung Research Institute, Colleges of Medicine and Public Health, The Ohio State University, Room 110, 473W 12th Avenue, 43210-1252, Columbus, OH, USA aut NATIONALLICENCE 700 1- Rajagopalan Sanjay Davis Heart and Lung Research Institute, Colleges of Medicine and Public Health, The Ohio State University, Room 110, 473W 12th Avenue, 43210-1252, Columbus, OH, USA aut NATIONALLICENCE 773 0- Inflammation Research SP Birkhäuser Verlag Basel 60/3(2011-03-01), 219-225 1023-3830 60:3<219 2011 60 11 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer