| RRC ID |
43137
|
| 著者 |
Chung SW, Toriba A, Chung HY, Yu BP, Kameda T, Tang N, Kizu R, Hayakawa K.
|
| タイトル |
Activation of 5-lipoxygenase and NF-kappa B in the action of acenaphthenequinone by modulation of oxidative stress.
|
| ジャーナル |
Toxicol Sci
|
| Abstract |
Quinoid polycyclic aromatic hydrocarbons are potent redox-active compounds that undergo enzymatic and nonenzymatic redox cycling with their semiquinone radical. We previously reported that acenaphthenequinone (AcQ) can damage human lung epithelial A549 cells through the formation of reactive species (RS). However, the biochemical mechanisms by which RS-generating enzymes cause oxidative burst during AcQ exposure remain elusive. Here we examined the biochemical mechanism of AcQ-induced RS generation by using selective metabolic inhibitors in A549 cells. We found that AA861, a 5-lipoxygenase (5-LO)-specific inhibitor significantly decreases RS generation. This inhibition of RS seems to be 5-LO specific because other inhibitors did not suppress AcQ-induced RS generation by nicotinamide adenine nucleotide phosphate (reduced) oxidase and/or xanthine oxidase. In addition, the inhibition of 5-LO by AA861 markedly reduced AcQ-induced nuclear factor kappa B (NF-kappa B) activation. We further found the activation of 5-LO pathway by exposing cells to AcQ mediates the secretion of inflammatory leukotriene B4, which can be significantly suppressed by a potent RS scavenger, N-acetylcysteine. Thus, based on our findings, we propose that AcQ-induced damage is likely due to increased RS generation and NF-kappa B activity through 5-LO activation.
|
| 巻・号 |
101(1)
|
| ページ |
152-8
|
| 公開日 |
2008-1-1
|
| DOI |
10.1093/toxsci/kfm252
|
| PII |
kfm252
|
| PMID |
17925309
|
| MeSH |
Acenaphthenes / pharmacology*
Acetylcysteine / pharmacology
Antioxidants / pharmacology
Arachidonate 15-Lipoxygenase / metabolism*
Benzoquinones / pharmacology
Biotransformation / drug effects
Blotting, Western
Cell Line, Tumor
Enzyme Activation / drug effects
Genes, Reporter / genetics
Humans
Immunoenzyme Techniques
Indicators and Reagents
Inflammation / physiopathology
Leukotriene B4 / metabolism
Luciferases / genetics
NF-kappa B / metabolism*
Oxidative Stress / drug effects*
Up-Regulation / drug effects
|
| IF |
3.703
|
| 引用数 |
9
|
|
WOS 分野
|
TOXICOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
A549(RCB0098) |
