The activation mechanism of the aryl hydrocarbon receptor (AhR) by molecular chaperone HSP90

The aryl hydrocarbon receptor is a member of the nuclear receptor superfamily that associates with the molecular chaperone HSP90 in the cytoplasm. The activation mechanism of the AhR is not yet fully understood. It has been proposed that after binding of ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3methylcholanthrene (3-MC), or β-naphthoflavone (β-NF), the AhR dissociates from HSP90 and translocates to the nucleus. It has also been hypothesized that the AhR translocates to the nucleus and forms a complex with HSP90 and other co-chaperones. There are a few reports about the direct association or dissociation of AhR and HSP90 due to difficulties in purifying AhR. We constructed and purified the PAS domain from AhR. Binding of the AhR-PAS domain to β-NF affinity resin suggested that it possesses ligand-binding affinity. We demonstrated that the AhR-PAS domain binds to HSP90 and the association is not affected by ligand binding. The ligand 17-DMAG inhibited binding of HSP90 to GST-PAS. In an immunoprecipitation assay, HSP90 was co-immunoprecipitated with AhR both in the presence or absence of ligand. Endogenous AhR decreased in the cytoplasm and increased in the nucleus of HeLa cells 15. min after treatment with ligand. These results suggested that the ligand-bound AhR is translocated to nucleus while in complex with HSP90.We used an in situ proximity ligation assay to confirm whether AhR was translocated to the nucleus alone or together with HSP90. HSP90 was co-localized with AhR after the nuclear translocation. It has been suggested that the ligand-bound AhR was translocated to the nucleus with HSP90. Activated AhR acts as a transcription factor, as shown by the transcription induction of the gene CYP1A1 8. h after treatment with β-NF

Efficacy of intraoperative fluorescence imaging using indocyanine green‐containing gauze in identifying the appropriate dissection layer in laparoscopic intersphincteric resection: A case report

Abstract In laparoscopic intersphincteric resection, identifying the dissection layer near the anus is often difficult. We safely proceeded with it, using indocyanine green‐containing gauze on the anal side to remove the internal anal sphincter with indocyanine green fluorography

The activation mechanism of the aryl hydrocarbon receptor (AhR) by molecular chaperone HSP90

The aryl hydrocarbon receptor is a member of the nuclear receptor superfamily that associates with the molecular chaperone HSP90 in the cytoplasm. The activation mechanism of the AhR is not yet fully understood. It has been proposed that after binding of ligands such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3methylcholanthrene (3-MC), or β-naphthoflavone (β-NF), the AhR dissociates from HSP90 and translocates to the nucleus. It has also been hypothesized that the AhR translocates to the nucleus and forms a complex with HSP90 and other co-chaperones. There are a few reports about the direct association or dissociation of AhR and HSP90 due to difficulties in purifying AhR. We constructed and purified the PAS domain from AhR. Binding of the AhR-PAS domain to β-NF affinity resin suggested that it possesses ligand-binding affinity. We demonstrated that the AhR-PAS domain binds to HSP90 and the association is not affected by ligand binding. The ligand 17-DMAG inhibited binding of HSP90 to GST-PAS. In an immunoprecipitation assay, HSP90 was co-immunoprecipitated with AhR both in the presence or absence of ligand. Endogenous AhR decreased in the cytoplasm and increased in the nucleus of HeLa cells 15 min after treatment with ligand. These results suggested that the ligand-bound AhR is translocated to nucleus while in complex with HSP90. We used an in situ proximity ligation assay to confirm whether AhR was translocated to the nucleus alone or together with HSP90. HSP90 was co-localized with AhR after the nuclear translocation. It has been suggested that the ligand-bound AhR was translocated to the nucleus with HSP90. Activated AhR acts as a transcription factor, as shown by the transcription induction of the gene CYP1A1 8 h after treatment with β-NF

Pyridone Alkaloids from a Marine-Derived Fungus, <i>Stagonosporopsis cucurbitacearum</i>, and Their Activities against Azole-Resistant <i>Candida albicans</i>

Four new 4-hydroxy-2-pyridone alkaloids, didymellamides A–D (<b>1</b>–<b>4</b>), were isolated from the marine-derived fungus <i>Stagonosporopsis cucurbitacearum</i>. The structures of <b>1</b>–<b>4</b> were elucidated from spectroscopic data (NMR, MS, and IR), and the absolute configuration of <b>1</b> was determined by X-ray diffraction analysis. Didymellamide A (<b>1</b>) exhibited antifungal activity against azole-resistant <i>Candida albicans.</i