Sensor systems of KEAP1 uniquely detecting oxidative and electrophilic stresses separately In vivo.

ABSTRACT: In the KEAP1-NRF2 stress response system, KEAP1 acts as a sensor for oxidative and electrophilic stresses through formation of S-S bond and C-S bond, respectively. Of the many questions left related to the sensor activity, following three appear important; whether these KEAP1 sensor systems are operating in vivo, whether oxidative and electrophilic stresses are sensed by the similar or distinct systems, and how KEAP1 equips highly sensitive mechanisms detecting oxidative and electrophilic stresses in vivo. To address these questions, we conducted a series of analyses utilizing KEAP1-cysteine substitution mutant mice, conditional selenocysteine-tRNA (Trsp) knockout mice, and human cohort whole genome sequence (WGS) data. Firstly, the Trsp-knockout provokes severe deficiency of selenoprotein

SUBMITTER: Sato M 

PROVIDER: S-EPMC11447412 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature