Cisplatin Inhibits AhR Activation

• 作者: Erina Sasaki-Kudoh Ewa Grave Hideaki Itoh Hiroaki Shimizu Ikuru Kudo Miki Hosaka Seiya Uemura Shun-Ichi Ikeda Shuntaro Togashi Taku Sugawara Yuka Kakizaki
• 来源期刊: 美国分子生物学期刊(英文)
• 学科: 医学
• 关键词: CISPLATIN CDDP AHR ARYL HYDROCARBON Receptor HSP90 17-DMAG
• 年，卷（期）: 2018,（1）
• 页码范围: 69-82
• 页数: 14页
• 分类号: R73

摘要

The AhR binds to contain ligands, such as 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin, 3-methylcholantrene, or β-naphthoflavone. The activation mechanism of AhR is not yet fully understood, but it is known that AhR associates with the molecular chaperone HSP90 in the cytoplasm. There are a few reports about the association or dissociation of AhR and HSP90, and which domain of HSP90 binds to AhR. We reported the association and activation mechanisms between HSP90 and AhR-PAS or AhR-bHLH. In the current study, we found that cisplatin inhibits the AhR activation. Although ATP and 17-DMAG have no effect on the dissociation of HSP90 from AhR, some contents of HSP90 were dissociated from AhR in the presence of cisplatin. We could detect the increase of CYP1A in the presence of 3-MC. On the contrary, the induction of CYP1A1 was inhibited in the presence of cisplatin. We couldn’t detect AhR in the HeLa cell soluble fraction in the presence of 50 μM cisplatin. In the presence of MG-132, we could detect AhR. These results suggested that AhR was dissociated from the HSP90 chaperone complex and processed during the protein proteasome degradation system in the presence of cisplatin.