title: Activation mechanisms of endothelial NF-kappaB, IKK, and MAP kinase by tert-butyl hydroperoxide.
abstract: Lipid peroxidation plays a major role in vascular dysfunction and age-related cardiovascular diseases. A major product of lipid peroxidation, tert-butyl hydroperoxide (t-BHP), has been reported to modulate vascular reactivity and cellular signaling. To better understand vascular abnormality, we set out to delineate the activation mechanism of nuclear factor kappa B (NF-kappaB) by t-BHP and the regulation of MAPK in endothelial cells. The results showed that t-BHP induces NF-kappaB activation by an inhibitor of kappaB (IkappaB) phosphorylation through IkappaB kinase (IKK) activation. Our data from this t-BHP study also showed increased p38 MAP kinase and ERK activity; however, interestingly, t-BHP showed no influence on JNK. Pretreatment with the p38 MAP kinase inhibitor, SB203580 and the ERK1/2 inhibitor, PD98059, prevented t-BHP-induced increases in p65 translocation, NF-kappaB luciferase activity, and phospho-IKKalpha/beta. Data suggested that t-BHP induces NF-kappaB activation through the IKK pathway, which involves p38 MAPK and ERK activation. This study illustrates a role of t-BHP in NF-kappaB activation and MAPK related-signaling pathways. The t-BHP-induced activation of NF-kappaB and MAPK could be a major player in vascular dysfunctions, as seen in oxidative stressed responses and the vascular inflammatory process.
authors: Genetic Engineering Research Institute, Aging Tissue Bank, Pusan National University, Busan 609-735, North Korea.
authors: Ji Young
authors: JY
authors: Lee
authors: Byung Pal
authors: BP
authors: Yu
authors: Hae Young
authors: HY
authors: Chung
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051550:I-kappa B Kinase; D008297:Male; D018613:Microscopy, Confocal; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D016328:NF-kappa B / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017382:Reactive Oxygen Species / Q000032:analysis; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014162:Transfection; D020122:tert-Butylhydroperoxide / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D020122:tert-Butylhydroperoxide; D017346:Protein Serine-Threonine Kinases; D051550:I-kappa B Kinase; D020928:Mitogen-Activated Protein Kinases