1999
DOI: 10.1074/jbc.274.17.11611
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4-Hydroxynonenal Prevents NF-κB Activation and Tumor Necrosis Factor Expression by Inhibiting IκB Phosphorylation and Subsequent Proteolysis

Abstract: Extensively oxidized low density lipoprotein (ox-LDL), a modulator of atherogenesis, down-regulates the lipopolysaccharide (LPS)-induced activation of transcription factor NF-B. We investigated whether 4-hydroxynonenal (HNE), a prominent aldehyde component of ox-LDL, represents one of the inhibitory substances. NF-B activation by stimuli such as LPS, interleukin (IL)-1␤, and phorbol ester, but not tumor necrosis factor (TNF), was reversibly inhibited by HNE in a dose-dependent manner in human monocytic cells, … Show more

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Cited by 162 publications
(117 citation statements)
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References 67 publications
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“…One class of IkB metabolism blockers includes signaling molecules such as nitric oxide (NO) (Matthews et al, 1996), Extensively Oxidized Low Density Lipoprotein (ox-LDL) (Brand et al, 1997), 4-hydroxynonenal (HNE) (Page et al, 1999), estrogen (E2) (Sun et al, 1998), and prostaglandin A (Rossi et al, 1997). At least one of these inhibitors shows pathway-speci®c inhibition of NF-kB; HNE can inhibit LPS-, IL-1-and phorbol ester-induced activation of NF-kB, but not that induced by TNFa (Page et al, 1999).…”
Section: Signaling Molecules As Blockers Of Ikb Phosphorylation/ Degrmentioning
confidence: 99%
See 1 more Smart Citation
“…One class of IkB metabolism blockers includes signaling molecules such as nitric oxide (NO) (Matthews et al, 1996), Extensively Oxidized Low Density Lipoprotein (ox-LDL) (Brand et al, 1997), 4-hydroxynonenal (HNE) (Page et al, 1999), estrogen (E2) (Sun et al, 1998), and prostaglandin A (Rossi et al, 1997). At least one of these inhibitors shows pathway-speci®c inhibition of NF-kB; HNE can inhibit LPS-, IL-1-and phorbol ester-induced activation of NF-kB, but not that induced by TNFa (Page et al, 1999).…”
Section: Signaling Molecules As Blockers Of Ikb Phosphorylation/ Degrmentioning
confidence: 99%
“…At least one of these inhibitors shows pathway-speci®c inhibition of NF-kB; HNE can inhibit LPS-, IL-1-and phorbol ester-induced activation of NF-kB, but not that induced by TNFa (Page et al, 1999).…”
Section: Signaling Molecules As Blockers Of Ikb Phosphorylation/ Degrmentioning
confidence: 99%
“…Transfection of THP-1 Cells-In transfection studies pGL2-IL-8 (420 bp of the IL-8 promoter region), a firefly luciferase reporter plasmid, was utilized (30,31). This plasmid (1 g) was transiently co-transfected with 0.2 g of a constitutively active Renilla luciferase control plasmid, pRLtk (Promega, Mannheim, Germany), into THP-1 cells using a DEAE-dextran-based protocol (30,31).…”
Section: Methodsmentioning
confidence: 99%
“…PAGE and Western Blot Analysis-Cytosolic and nuclear extracts were isolated as described (4,39), and electrophoresis was performed with 12.5% polyacrylamide gels. The proteins were transferred to nitrocellulose membranes using the wet blot technique.…”
Section: Methodsmentioning
confidence: 99%
“…Immunoprecipitation-Cytosolic extracts were subjected to immunoprecipitation in TNT buffer (200 mM NaCl, 20 mM Tris-HCl, pH 7.5, 1% Triton X-100, 1 mM dithiothreitol, 0.5 M 4-(2-aminoethyl)-benzenesulfonyl fluoride, leupeptin, antipain, aprotinin, pepstatin A, chymostatin 0.75 g/ml each; Sigma) (4,39). Immunoprecipitation was carried out using 35 l of 6% protein A-or G-agarose (Roche Applied Science) for 2 h at 4°C with 1 g of anti-IKK␣ (BD Biosciences), IKK␤ (QED Bioscience), IKK␥ (Santa Cruz Biotechnology), or anti-FLAG antibody.…”
Section: Methodsmentioning
confidence: 99%