Modulation of Unfolded Protein Response by Methylmercury
| العنوان: | Modulation of Unfolded Protein Response by Methylmercury |
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| المؤلفون: | Yoshito Kumagai, Takashi Uehara, Shiori Akiyama, Kengo Nakahara, Yuki Kaneko, Kosaku Okuda, Masatake Fujimura, Nobumasa Takasugi, Takao Iwawaki, Hideki Hiraoka |
| المصدر: | Biological & Pharmaceutical Bulletin. 40:1595-1598 |
| بيانات النشر: | Pharmaceutical Society of Japan, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | X-Box Binding Protein 1, 0301 basic medicine, XBP1, Pharmaceutical Science, Mice, eIF-2 Kinase, 03 medical and health sciences, Animals, Protein kinase A, Protein disulfide-isomerase, Cell Nucleus, Pharmacology, Cell Death, Kinase, Chemistry, ATF6, Binding protein, Endoplasmic reticulum, Protein Disulfide Reductase (Glutathione), General Medicine, Methylmercury Compounds, Endoplasmic Reticulum Stress, Activating Transcription Factor 6, Cell biology, 030104 developmental biology, Unfolded Protein Response, Unfolded protein response |
| الوصف: | Methylmercury (MeHg) results in cell death through endoplasmic reticulum (ER) stress. Previously, we reported that MeHg induces S-mercuration at cysteine 383 or 386 in protein disulfide isomerase (PDI), and this modification induces the loss of enzymatic activity. Because PDI is a key enzyme for the maturation of nascent protein harboring a disulfide bond, the disruption in PDI function by MeHg results in ER stress via the accumulation of misfolded proteins. However, the effects of MeHg on unfolded protein response (UPR) sensors and their signaling remain unclear. In the present study, we show that UPR is regulated by MeHg. We found that MeHg specifically attenuated inositol-requiring enzyme 1α (IRE1α)–x-box binding protein 1 (XBP1) branch, but not the protein kinase RNA-like endoplasmic reticulum kinase (PERK) and activating transcriptional factor 6 (ATF6) branches. Treatment with GSK2606414, a specific PERK inhibitor, significantly inhibited MeHg-induced cell death. These findings suggest that MeHg exquisitely regulates UPR signaling involved in cell death. |
| وصف الملف: | application/pdf |
| تدمد: | 1347-5215 0918-6158 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f61e47f74080162d41564b6560fe9164 https://doi.org/10.1248/bpb.b17-00359 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....f61e47f74080162d41564b6560fe9164 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 13475215 09186158 |
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