TY - JOUR
T1 - The emerging role of electrophiles as a key regulator for endoplasmic reticulum (Er) stress
AU - Takasugi, Nobumasa
AU - Hiraoka, Hideki
AU - Nakahara, Kengo
AU - Akiyama, Shiori
AU - Fujikawa, Kana
AU - Nomura, Ryosuke
AU - Furuichi, Moeka
AU - Uehara, Takashi
N1 - Funding Information:
Funding: This work was supported in part by a Grants-in-Aid for Scientific Research (B) 18H02579, Challenging Exploratory Research 17K19490, Scientific Research (S) 17H06170, 18H05293 (to T.U.), and Scientific Research (C) 17K08272 (to N.T.) from the Ministry of Education, Culture, Sports and Technology (MEXT) of Japan, and the Smoking Research Foundation (to T.U.) and Life Science Foundation of Japan (to N.T.).
Publisher Copyright:
© 2019 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2019/4/1
Y1 - 2019/4/1
N2 - The unfolded protein response (UPR) is activated by the accumulation of misfolded proteins in the endoplasmic reticulum (ER), which is called ER stress. ER stress sensors PERK, IRE1, and ATF6 play a central role in the initiation and regulation of the UPR; they inhibit novel protein synthesis and upregulate ER chaperones, such as protein disulfide isomerase, to remove unfolded proteins. However, when recovery from ER stress is difficult, the UPR pathway is activated to eliminate unhealthy cells. This signaling transition is the key event of many human diseases. However, the precise mechanisms are largely unknown. Intriguingly, reactive electrophilic species (RES), which exist in the environment or are produced through cellular metabolism, have been identified as a key player of this transition. In this review, we focused on the function of representative RES: nitric oxide (NO) as a gaseous RES, 4-hydroxynonenal (HNE) as a lipid RES, and methylmercury (MeHg) as an environmental organic compound RES, to outline the relationship between ER stress and RES. Modulation by RES might be a target for the development of next-generation therapy for ER stress-associated diseases.
AB - The unfolded protein response (UPR) is activated by the accumulation of misfolded proteins in the endoplasmic reticulum (ER), which is called ER stress. ER stress sensors PERK, IRE1, and ATF6 play a central role in the initiation and regulation of the UPR; they inhibit novel protein synthesis and upregulate ER chaperones, such as protein disulfide isomerase, to remove unfolded proteins. However, when recovery from ER stress is difficult, the UPR pathway is activated to eliminate unhealthy cells. This signaling transition is the key event of many human diseases. However, the precise mechanisms are largely unknown. Intriguingly, reactive electrophilic species (RES), which exist in the environment or are produced through cellular metabolism, have been identified as a key player of this transition. In this review, we focused on the function of representative RES: nitric oxide (NO) as a gaseous RES, 4-hydroxynonenal (HNE) as a lipid RES, and methylmercury (MeHg) as an environmental organic compound RES, to outline the relationship between ER stress and RES. Modulation by RES might be a target for the development of next-generation therapy for ER stress-associated diseases.
KW - 4-hydroxynonenal
KW - ER stress
KW - Methylmercury
KW - Nitric oxide
KW - Reactive electrophiles
KW - UPR
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U2 - 10.3390/ijms20071783
DO - 10.3390/ijms20071783
M3 - Review article
C2 - 30974903
AN - SCOPUS:85064844715
SN - 1661-6596
VL - 20
JO - International journal of molecular sciences
JF - International journal of molecular sciences
IS - 7
M1 - 1783
ER -
