The emerging role of electrophiles as a key regulator for endoplasmic reticulum (Er) stress

Nobumasa Takasugi, Hideki Hiraoka, Kengo Nakahara, Shiori Akiyama, Kana Fujikawa, Ryosuke Nomura, Moeka Furuichi, Takashi Uehara

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

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.

Original languageEnglish
Article number1783
JournalInternational journal of molecular sciences
Volume20
Issue number7
DOIs
Publication statusPublished - Apr 1 2019

Fingerprint

endoplasmic reticulum
Endoplasmic Reticulum Stress
regulators
emerging
Unfolded Protein Response
Proteins
proteins
Endoplasmic Reticulum
Protein Disulfide-Isomerases
Protein Unfolding
protein synthesis
Nitric Oxide
Organic compounds
Metabolism
Up-Regulation
Nitric oxide
disulfides
metabolism
nitric oxide
organic compounds

Keywords

  • 4-hydroxynonenal
  • ER stress
  • Methylmercury
  • Nitric oxide
  • Reactive electrophiles
  • UPR

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

The emerging role of electrophiles as a key regulator for endoplasmic reticulum (Er) stress. / Takasugi, Nobumasa; Hiraoka, Hideki; Nakahara, Kengo; Akiyama, Shiori; Fujikawa, Kana; Nomura, Ryosuke; Furuichi, Moeka; Uehara, Takashi.

In: International journal of molecular sciences, Vol. 20, No. 7, 1783, 01.04.2019.

Research output: Contribution to journalReview article

Takasugi, Nobumasa ; Hiraoka, Hideki ; Nakahara, Kengo ; Akiyama, Shiori ; Fujikawa, Kana ; Nomura, Ryosuke ; Furuichi, Moeka ; Uehara, Takashi. / The emerging role of electrophiles as a key regulator for endoplasmic reticulum (Er) stress. In: International journal of molecular sciences. 2019 ; Vol. 20, No. 7.
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