PMID- 28237703 OWN - NLM STAT- MEDLINE DCOM- 20170613 LR - 20171127 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 485 IP - 2 DP - 2017 Apr 1 TI - Effect of cellular ubiquitin levels on the regulation of oxidative stress response and proteasome function via Nrf1. PG - 234-240 LID - S0006-291X(17)30396-0 [pii] LID - 10.1016/j.bbrc.2017.02.105 [doi] AB - The polyubiquitin genes Ubb and Ubc are upregulated under oxidative stress induced by arsenite [As(III)]. However, the role of ubiquitin (Ub) under As(III) exposure is not known in detail. In a previous study, we showed that the reduced viability observed in Ubc(-/-) mouse embryonic fibroblasts under As(III) exposure was not due to dysregulation of the Nrf2-Keap1 pathway, which prompted us to investigate another NFE2 family protein, nuclear factor erythroid 2-related factor 1 (Nrf1). In this study, we found that Ub deficiency due to Ubc knockdown in N2a cells reduced cell viability and proteasome activity under As(III) exposure. Furthermore, mRNA levels of the proteasome subunit Psma1 were also reduced. In addition, Ub deficiency led to the nuclear accumulation of the p65 isoform of Nrf1 under As(III) exposure. Interestingly, the overexpression of p65-Nrf1 recapitulated the phenotypes of Ub-deficient N2a cells under As(III) exposure. On the other hand, Nrf1 knockdown suppressed the death of Ub-deficient N2a cells upon exposure to As(III). Therefore, the levels of p65-Nrf1 may play an important role in the maintenance of cell viability under oxidative stress induced by As(III). CI - Copyright (c) 2017 Elsevier Inc. All rights reserved. FAU - Lee, Donghee AU - Lee D AD - Department of Life Science, University of Seoul, Seoul 02504, Republic of Korea. FAU - Ryu, Kwon-Yul AU - Ryu KY AD - Department of Life Science, University of Seoul, Seoul 02504, Republic of Korea. Electronic address: kyryu@uos.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20170222 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Arsenites) RN - 0 (Nrf1 protein, mouse) RN - 0 (Nuclear Respiratory Factor 1) RN - 0 (Ubiquitin) RN - 0 (Ubiquitin C) RN - EC 3.4.25.1 (Proteasome Endopeptidase Complex) RN - N5509X556J (arsenite) SB - IM MH - Animals MH - Arsenites/*toxicity MH - Cell Line MH - Cell Survival/drug effects MH - Gene Expression Regulation/drug effects MH - Gene Knockdown Techniques MH - Mice MH - NIH 3T3 Cells MH - Nuclear Respiratory Factor 1/genetics/*metabolism MH - Oxidative Stress/*drug effects MH - Proteasome Endopeptidase Complex/genetics/*metabolism MH - Ubiquitin/genetics/*metabolism MH - Ubiquitin C/genetics/metabolism OTO - NOTNLM OT - Arsenite OT - Nrf1 OT - Oxidative stress OT - Polyubiquitin gene OT - Proteasome OT - Ubiquitin EDAT- 2017/02/27 06:00 MHDA- 2017/06/14 06:00 CRDT- 2017/02/27 06:00 PHST- 2017/02/15 00:00 [received] PHST- 2017/02/20 00:00 [accepted] PHST- 2017/02/27 06:00 [pubmed] PHST- 2017/06/14 06:00 [medline] PHST- 2017/02/27 06:00 [entrez] AID - S0006-291X(17)30396-0 [pii] AID - 10.1016/j.bbrc.2017.02.105 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2017 Apr 1;485(2):234-240. doi: 10.1016/j.bbrc.2017.02.105. Epub 2017 Feb 22.