ID | 64238 |
FullText URL | |
Author |
Nomura, Ryosuke
Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Takasugi, Nobumasa
Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Hiraoka, Hideki
Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Iijima, Yuta
Department of Medicinal Pharmacology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
Iwawaki, Takao
Division of Cell Medicine, Department of Life Science, Medical Research Institute, Kanazawa Medical University
Kumagai, Yoshito
Environmental Biology Laboratory, Faculty of Medicine, University of Tsukuba
Fujimura, Masatake
Department of Basic Medical Science, National Institute for Minamata Disease
|
Abstract | Methylmercury (MeHg), an environmental toxicant, induces neuronal cell death and injures specific areas of the brain. MeHg is known to induce oxidative and endoplasmic reticulum (ER) stress. The unfolded protein response (UPR) pathway has a dual nature in that it regulates and protects cells from an overload of improperly folded proteins in the ER, whereas excessively stressed cells are eliminated by apoptosis. Oxidative stress/ER stress induced by methylmercury exposure may tilt the UPR toward apoptosis, but there is little in vivo evidence of a direct link to actual neuronal cell death. Here, by using the ER stress-activated indicator (ERAI) system, we investigated the time course signaling alterations of UPR in vivo in the most affected areas, the somatosensory cortex and striatum. In the ERAI-Venus transgenic mice exposed to MeHg (30 or 50 ppm in drinking water), the ERAI signal, which indicates the activation of the cytoprotective pathway of the UPR, was only transiently enhanced, whereas the apoptotic pathway of the UPR was persistently enhanced. Furthermore, detailed analysis following the time course showed that MeHg-induced apoptosis is strongly associated with alterations in UPR signaling. Our results suggest that UPR modulation could be a therapeutic target for treating neuropathy.
|
Keywords | methylmercury
neuronal cell death
endoplasmic reticulum stress
unfolded protein response
ERAI system
|
Published Date | 2022-12-06
|
Publication Title |
International Journal Of Molecular Sciences
|
Volume | volume23
|
Issue | issue23
|
Publisher | MDPI
|
Start Page | 15412
|
ISSN | 1422-0067
|
Content Type |
Journal Article
|
language |
English
|
OAI-PMH Set |
岡山大学
|
Copyright Holders | © 2022 by the authors.
|
File Version | publisher
|
PubMed ID | |
DOI | |
Web of Science KeyUT | |
Related Url | isVersionOf https://doi.org/10.3390/ijms232315412
|
License | https://creativecommons.org/licenses/by/4.0/
|