Induction of REDD1 via AP-1 prevents oxidative stress-mediated injury in hepatocytes.

Induction of REDD1 via AP-1 prevents oxidative stress-mediated injury in hepatocytes. Free Radic Biol Med. 2018 Jun 14;: Authors: Cho SS, Kim KM, Yang JH, Kim JY, Park SJ, Kim SJ, Kim JK, Cho IJ, Ki SH Abstract Regulated in development and DNA damage responses 1 (REDD1) is an inducible gene in response to various stresses, which functions as a negative regulator of the mammalian target of rapamycin protein kinase in complex 1. In the present study, we identified the role of REDD1 under the oxidative stress-mediated hepatocyte injury and its regulatory mechanism. REDD1 protein was increased in H2O2 or tert-butylhydroperoxide (t-BHP)-treated hepatocytes. H2O2 also elevated REDD1 mRNA levels. This event was inhibited by antioxidants such as diphenyleneiodonium chloride, N-acetyl-L-cysteine, or butylated hydroxy anisole. Interestingly, we found that H2O2-mediated REDD1 induction was transcriptionally regulated by activator protein-1 (AP-1), and that overexpression of c-Jun increased REDD1 protein levels and REDD1 promoter-driven luciferase activity. Deletion of the putative AP-1 binding site in proximal region of the human REDD1 promoter significantly abolished REDD1 transactivation by c-Jun. A NF-E2-related factor 2 activator, tert-butylhydroquinone treatment also elevated REDD1 levels, but it was independent on NF-E2-related factor 2 activation. Furthermore, we observed that REDD1 overexpression attenuated H2O2 or t-BHP-derived reactiv...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research