Activation of NF-κB by Palmitate in Endothelial Cells

• DOI: 10.1161/atvbaha.109.188813
• Publication Date: 2009-06-19T02:11:28Z
• Authors: Ezekiel Maloney; Ian R. Sweet; David M. Hockenbery; Matilda Pham; Norma O. Rizzo; Sanshiro Tateya; Priya Handa; Michael W. Schwartz; Francis Kim
• Keywords: NOX4

Objective— We investigated whether NADPH oxidase–dependent production of superoxide contributes to activation NF-κB in endothelial cells by the saturated free fatty acid palmitate. Methods and Results— After incubation human with palmitate at a concentration known induce cellular inflammation (100 μmol/L), we measured levels using electron spin resonance spectroscopy trap 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH). Palmitate exposure induced >2-fold increase levels, an effect associated signaling as phospho-IκBα, activity, IL-6, ICAM expression. Reduction each 3 different interventions—pretreatment dismutase (SOD), diphenylene iodinium (DPI), or knockdown oxidase 4 (NOX4) siRNA—attenuated palmitate-mediated signaling. Inhibition toll like receptor-4 (TLR4) also suppressed inflammation, whereas was not affected overexpression phosphorylation mutant IκBα (NF-κB super repressor) that blocks downstream IKKβ/NF-κB. Finally, high-fat feeding increased expression NOX4 upstream activator, bone morphogenic protein (BMP4), thoracic aortic tissue from C57BL/6 mice, but TLR4 −/− compared low-fat fed controls. Conclusions— These results suggest links palmitate-stimulated cells.