Yangonin blocks tumor necrosis factor-α-induced nuclear factor-κB-dependent transcription by inhibiting the transactivation potential of the RelA/p65 subunit
| Autor: | Ji-Xing Nan, He Liang, Xuejun Jin, Ying Zi Jiang, Donghao Li, Jung Joon Lee, Xue Wu, Juan Ma, Hong Ri Jin, Nguyen Tien Dat, Shan Yu Zhang |
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| Rok vydání: | 2012 |
| Předmět: |
Transcriptional Activation
p38 mitogen-activated protein kinases Biology Transactivation chemistry.chemical_compound Mice Animals Humans Yangonin Protein kinase A Transcription factor Pharmacology RELA Dose-Response Relationship Drug Kinase Tumor Necrosis Factor-alpha lcsh:RM1-950 NF-kappa B Transcription Factor RelA Molecular biology IκBα Protein Subunits lcsh:Therapeutics. Pharmacology chemistry Pyrones Molecular Medicine HeLa Cells |
| Zdroj: | Journal of Pharmacological Sciences, Vol 118, Iss 4, Pp 447-454 (2012) |
| ISSN: | 1347-8648 |
| Popis: | The nuclear factor-κB (NF-κB) transcription factors control many physiological processes including inflammation, immunity, and apoptosis. In our search for NF-κB inhibitors from natural resources, we identified yangonin from Piper methysticum as an inhibitor of NF-κB activation. In the present study, we demonstrate that yangonin potently inhibits NF-κB activation through suppression of the transcriptional activity of the RelA/p65 subunit of NF-κB. This compound significantly inhibited the induced expression of the NF-κB-reporter gene. However, this compound did not interfere with tumor necrosis factor-α (TNF-α)-induced inhibitor of κBα (IκBα) degradation, p65 nuclear translocation, and DNA-binding activity of NF-κB. Further analysis revealed that yangonin inhibited not only the induced NF-κB activation by overexpression of RelA/p65, but also transactivation activity of RelA/p65. Moreover, yangonin did not inhibit TNF-α-induced activation of p38, but it significantly impaired activation of extracellular signal-regulated kinase 1/2 and stress-activated protein kinase/c-Jun NH2-terminal kinase. We also demonstrated that pretreatment of cells with this compound prevented TNF-α-induced expression of NF-κB target genes, such as interleukin 6, interleukin 8, monocyte chemotactic protein 1, cyclooxygenase-2 and inducible nitric oxide. Taken together, yangonin could be a valuable candidate for the intervention of NF-κB-dependent pathological conditions such as inflammation. Keywords:: yangonin, nuclear factor-κB (NF-κB), RelA/p65, transactivation, inflammation |
| Databáze: | OpenAIRE |
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