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Sestrin2 Gene Induction by Nrf2‐ARE Pathway
Author(s) -
Ki Sung Hwan,
Shin Bo Yeon,
Jin So Hee,
Cho Je
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb596
Subject(s) - gene knockdown , gene , transcription factor , gene expression , microbiology and biotechnology , regulation of gene expression , biology , chemistry , genetics
The Sestrin2 (Sesn2) gene encodes a conserved antioxidant protein that is induced upon oxidative stress and protects cells against ROS. Nrf2 is an essential transcription factor that regulates expression of a variety of antioxidant genes via binding to the antioxidant‐response element (ARE), but the role of Nrf2 in Sesn2 gene expression has not been elucidated yet. The present study investigated whether the Nrf2‐ARE pathway regulates Sesn2 gene expression and the identification of the molecular mechanism. The Nrf2 activators up‐regulated Sesn2 expression in a dose‐and time‐dependent manner in hepatocytes. The specific role of Nrf2 in Sesn2 induction was verified by using Nrf2 over‐expression plasmid and Nrf2 knockout or knockdown cells. In silico analysis of the 5′ upstream region of Sesn2 gene identified a putative ARE sequence. Deletion of the putative ARE demonstrated that ARE from −550 to −539 bp in the human Sesn2 promoter was critical for the Nrf2‐mediated response. Knockdown experiments with Sesn2 siRNA showed that Sesn2 is required for the Nrf2‐mediated cytoprotective activity against hydrogen peroxide. Our results suggest that the Nrf2‐ARE pathway is critical for Sesn2 gene expression and might protect against oxidative stress. This research was supported by the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (No. R13‐2008‐010‐‐0)