Journal
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY
Volume 44, Issue 8, Pages 1315-1320Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.biocel.2012.04.021
Keywords
Nrf2-Keap1 pathway; Proteasome; Oxidative stress; ER stress; Antioxidant defenses
Categories
Funding
- Heart Research UK
- Henry Smith Charity (UK)
- British Heart Foundation
- EU FOD-CC
- Great Britain Sasakawa Foundation
Ask authors/readers for more resources
Excessive reactive oxygen species (ROS) generation is as a major cause of oxidative stress and is implicated in cellular dysfunction in aging, cardiovascular disease and other pathologies. As antioxidant trials have largely failed to provide protection in humans, research focus has shifted to activating endogenous antioxidant defenses. In vascular models, activators of the transcription factor NF-E2 related factor 2 (Nrf2) pathway have been shown to restore redox homeostasis by increasing antioxidant/electrophilic response element-mediated (ARE/EpRE) expression of phase II and antioxidant enzymes, including NAD(P)H:quinone oxidoreductase-1 (NQO1), heme oxygenase-1 (HO-1) and gamma-glutamate cysteine ligase catalytic subunit (GCLC). Nrf2 activators disrupt basal ubiquitin-dependent degradation of Nrf2 by the 265 proteasome, leading to nuclear Nrf2 accumulation and gene induction. This review examines the evidence for crosstalk between Nrf2 and the proteasome, highlighting the mechanisms by which select Nrf2 activators regulate stress-induced proteasomal activity and removal of oxidized proteins. Exploiting the dual action of natural Nrf2 inducers may provide a novel therapeutic strategy for restoring cellular redox homeostasis in aging and cardiovascular related diseases such diabetes, atherosclerosis and stroke. (C) 2012 Elsevier Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available