Anti-osteoclastic effect of caffeic acid phenethyl ester in murine macrophages depends upon the suppression of superoxide anion production through the prevention of an active-Nox1 complex formation
| Autor: | Yong-Beom Kwon, Hae-Dong Jang, Fang-Fang Wang |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
rac1 GTP-Binding Protein Endocrinology Diabetes and Metabolism Clinical Biochemistry Osteoclasts Biochemistry 03 medical and health sciences chemistry.chemical_compound Mice Caffeic Acids Superoxides Animals Bone Resorption Caffeic acid phenethyl ester Molecular Biology Nutrition and Dietetics Dose-Response Relationship Drug Kinase Superoxide Activator (genetics) Neuropeptides RANK Ligand NF-kappa B NADPH Oxidases Phenylethyl Alcohol Molecular biology Transcription Factor AP-1 IκBα Protein Transport 030104 developmental biology RAW 264.7 Cells chemistry NOX1 Multiprotein Complexes NADPH Oxidase 1 Signal transduction Nicotinamide adenine dinucleotide phosphate |
| Zdroj: | The Journal of nutritional biochemistry. 58 |
| ISSN: | 1873-4847 |
| Popis: | This study investigated the anti-osteoclastic effect of caffeic acid phenethyl ester (CAPE) through suppression of Nox1-mediated superoxide anions production. The multi-nucleated cells were counted and followed by measuring their tartrate-resistant acid phosphatase (TRAP) activity. The superoxide anion production was determined by using fluorescent probe dihydroethidium (DHE). After one day of exposure to the receptor activator of nuclear factor-κB ligand (RANKL), the expression of the proteins involved in superoxide anion production was determined by western blotting. A potent anti-osteoclastic effect of CAPE was observed; the superoxide anion level reached a maximum value after one day of incubation. CAPE attenuated the expression of NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 1 (Nox1) and Rac1, and mitigated the RANKL-induced translocation of p47phox to the cell membrane. In addition, CAPE suppressed the expression of nuclear factor-kappa B (NF-κB p65), its translocation to the nucleus, and the activation of NF-κB inhibitor (IκBα) and its kinase (IKKβ). Furthermore, CAPE diminished the expression and activation of the c-jun N-terminal kinase (JNK) and the expression of protein-1 activators (AP-1) such as c-Fos and c-Jun. The expression of Nox1 was suppressed by CAPE through the down-regulation of IKKβ/IκBα/NF-κB and JNK/AP-1 signal pathway. This study provides evidence that the anti-osteoclastic effect of CAPE depends upon the attenuated superoxide anion production, which is closely related with interruption of an active Nox1 complex formation due to the attenuated catalytic subunit Nox1 expression resulting from suppression of the IKKβ/IκBα/NF-κB and JNK/AP-1 signaling pathway and the down-regulation of the p47phox subunit translocation to the cell membrane. |
| Databáze: | OpenAIRE |
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