Taurochenodeoxycholic Acid Inhibited AP-1 Activation via Stimulating Glucocorticoid Receptor

Li, Lei; Liu, Chang; Mao, Wei; Tumen, Bayaer; Li, Peifeng

doi:10.3390/molecules24244513

Cited by 22 publications

(13 citation statements)

References 40 publications

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“…Then samples freeze‐dried and then dissolved in 2 ml of methanol. Finally, all samples were examined using a spectrophotometer to determine the quantity of releasing embelin …”

Section: Methodsmentioning

confidence: 99%

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Antiarthritic effect of chitosan nanoparticle loaded with embelin against adjuvant‐induced arthritis in Wistar rats

Cui

Sreeharsha

et al. 2020

IUBMB Life

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Background Rheumatoid arthritis (RA) is associated with joint damage. Effectiveness of embelin has been established in a wide variety of inflammatory disorders, but its utility as a therapeutic agent is limited by its poor absorption, rapid metabolism, and fast systemic elimination. To apprehend these limitations, we propose to use highly bioavailable embelin‐loaded chitosan nanoparticles (CS‐embelin NPs) for the treatment of RA. Methods The rats were made arthritic using a subcutaneous injection with 0.1 ml complete Freund's adjuvant (CFA) into the footpad of the left hind paw. CS‐embelin NPs (25 and 50 mg/kg) was administered from day 15 to day 28 after adjuvant injection. After the experimental period, the animals were sacrificed and various biochemical markers were assessed. Results Arthritic score and paw swelling were significantly reduced after treatment with CS‐embelin NPs. Arthritis‐induced rats showed a significant increase in malondialdehyde (MDA) and nitric oxide (NO) with a concomitant reduction of antioxidants in the paw tissue. CS‐embelin NPs (25 and 50 mg/kg) reduced MDA and NO levels and restored antioxidant levels to normalcy by mitigating oxidative stress. The arthritic rats exhibited elevated tumor necrosis factor‐α (TNF‐α), interleukin‐6 (IL‐6) and interleukin‐1beta (IL‐1β) serum concentrations, upregulated TNF‐ α and IL–6 protein levels and upregulated nuclear factor‐kB (NF‐kB) mRNA expression in paw tissues. Treatment with CS‐embelin NPs (25 and 50 mg/kg) significantly reduced serum levels and down‐regulated inflammatory markers to normalcy, dose‐dependently. Conclusion The results suggest that CS‐embelin NPs displayed a protective effect against adjuvant‐induced arthritis in rats mediated through antioxidant and anti‐inflammatory effects.

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“…Then samples freeze‐dried and then dissolved in 2 ml of methanol. Finally, all samples were examined using a spectrophotometer to determine the quantity of releasing embelin …”

Section: Methodsmentioning

confidence: 99%

“…Finally, all samples were examined using a spectrophotometer to determine the quantity of releasing embelin. 25…”

Section: Measurement Of Embelin Release Profile From Nanoparticlesmentioning

confidence: 99%

Antiarthritic effect of chitosan nanoparticle loaded with embelin against adjuvant‐induced arthritis in Wistar rats

Cui

Sreeharsha

et al. 2020

IUBMB Life

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“…The loss of AP-1 significantly reduces the binding of GR to the DNA. 33,34 This could be due to the fact that GR must bind with AP-1 to bind the DNA or because of the increased chromatin accessibility established by the activation of AP-1. In addition, AP-1 is recruited to the TR responsive element (TRE) inflammatory gene to induce transcription and serves as a pioneer for the subsequent recruitment of GR.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, AP-1 is recruited to the TR responsive element (TRE) inflammatory gene to induce transcription and serves as a pioneer for the subsequent recruitment of GR. 33,34 Regulators that involve in GR binding may be cell type-specific. The AP-1 motif was identified at the GR-binding site in hepatocytes, and the enrichment of motifs for other proteins (e.g.…”

Section: Discussionmentioning

confidence: 99%

Cell-specific expression of ENACα gene by FOXA1 in the glucocorticoid receptor pathway

Chung

Jin

Jeong

2020

Int J Immunopathol Pharmacol

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Introduction: The glucocorticoid receptor (GR) is one of the most widely studied ligand-dependent nuclear receptors. The combination of transcriptional regulatory factors required for the expression of individual genes targeted by GR varies across cell types; however, the mechanisms underlying this cell type–specific regulation of gene expression are not yet clear. Methods: Here, we investigated genes regulated by GR in two different cell lines, A549 and ARPE-19, and examined how gene expression varied according to the effect of pioneer factors using RNA-seq and RT-qPCR. Results: Our RNA-seq results identified 19 and 63 genes regulated by GR that are ARPE-19-specific and A549-specific, respectively, suggesting that GR induces the expression of different sets of genes in a cell type–specific manner. RT-qPCR confirmed that the epithelial sodium channel ( ENACα) gene is an ARPE-19 cell-specific GR target gene, whereas the FK506 binding protein 5 ( FKBP5) gene was A549 cell-specific. There was a significant decrease in ENACα expression in FOXA1-deficient ARPE-19 cells, suggesting that FOXA1 might function as a pioneer factor enabling the selective expression of ENACα in ARPE-19 cells but not in A549 cells. Conclusion: These findings indicate that ENACα expression in ARPE-19 cells is regulated by FOXA1 and provide insights into the molecular mechanisms of cell type–specific expression of GR-regulated genes.

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“… Rouleau et al (1995) and MacLeod et al (1995) found, in Y1 cells derived from a naturally occurring adrenocortical tumor in LAF1 mice, Ras-activator protein 1 (AP-1) (c-Jun) pathway could regulate the activity of DNMT, then influencing DNA methylation ( Rouleau et al, 1995 ). AP-1 is a transcription factor composed of homo- and/or heterodimers of Jun and Fos proteins ( Li et al, 2019 ). The phosphorylation of AP-1 can induce their activation, and then they have transcriptional activity into the nucleus, and c-Jun is activated through phosphorylation by the c-Jun N-terminal kinase (JNK) ( Gupta et al, 1996 ; Kallunki et al, 1996 ).…”

Section: Introductionmentioning

confidence: 99%

Farnesyl Transferase Inhibitor Lonafarnib Enhances α7nAChR Expression Through Inhibiting DNA Methylation of CHRNA7 and Increases α7nAChR Membrane Trafficking

et al. 2020

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Inhibition of Ras farnesylation in acute has been found to upregulate the α7 nicotinic acetylcholine receptor (α7nAChR) activity. This study was carried out to investigate the effect of chronic administration for 7 days of farnesyl transferase inhibitor lonafarnib (50 mg/kg, intraperitoneally injected) to male mice on the expression and activity of α7nAChR in hippocampal CA1 pyramidal cells. Herein, we show that lonafarnib dose dependently enhances the amplitude of ACh-evoked inward currents (IACh), owning to the increased α7nAChR expression and membrane trafficking. Lonafarnib inhibited phosphorylation of c-Jun and JNK, which was related to DNA methylation. In addition, reduced DNA methyltransferase 1 (DNMT1) expression was observed in lonafarnib-treated mice, which was reversed by JNK activator. Lonafarnib-upregulated expression of α7nAChR was mimicked by DNMT inhibitor, and repressed by JNK activator. However, only inhibited DNA methylation did not affect IACh, and the JNK activator partially decreased the lonafarnib-upregulated IACh. On the other hand, lonafarnib also increased the membrane expression of α7nAChR, which was partially inhibited by JNK activator or CaMKII inhibitor, without changes in the α7nAChR phosphorylation. CaMKII inhibitor had no effect on the expression of α7nAChR. Lonafarnib-enhanced spatial memory of mice was also partially blocked by JNK activator or CaMKII inhibitor. These results suggest that Ras inhibition increases α7nAChR expression through depressed DNA methylation of CHRNA7 via Ras-c-Jun-JNK pathway, increases the membrane expression of α7nAChR resulting in part from the enhanced CaMKII pathway and total expression of this receptor, and consequently enhances the spatial memory.

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Taurochenodeoxycholic Acid Inhibited AP-1 Activation via Stimulating Glucocorticoid Receptor

Cited by 22 publications

References 40 publications

Antiarthritic effect of chitosan nanoparticle loaded with embelin against adjuvant‐induced arthritis in Wistar rats

Antiarthritic effect of chitosan nanoparticle loaded with embelin against adjuvant‐induced arthritis in Wistar rats

Cell-specific expression of ENACα gene by FOXA1 in the glucocorticoid receptor pathway

Farnesyl Transferase Inhibitor Lonafarnib Enhances α7nAChR Expression Through Inhibiting DNA Methylation of CHRNA7 and Increases α7nAChR Membrane Trafficking

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