Role Of Nrf2 In Oxidative Stress And Toxicity Pdf

role of nrf2 in oxidative stress and toxicity pdf

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Typically in aerobic metabolism, organic compounds such as nucleic acids, proteins and lipids can undergo structural damage by oxidative reactions. Various diseases such as cancer, diabetes, cardiovascular diseases and neurodegenerative clearly exemplify the chronic oxidative stress. Therefore, it is important to consider that at low and moderate ROS levels, it can, for example, act as signaling molecules that support cell proliferation and differentiation and activate survival pathways in response to stress. Correlations between oxidative stress and disease should be carefully investigated in order to understand whether oxidative stress actually increases susceptibility to a particular disease or opposite.

Potential Protective and Therapeutic Roles of the Nrf2 Pathway in Ocular Diseases: An Update

Han K. Ho, Collin C. Kavanagh, Sidney D. Nelson, Sam A. A functional correlate was also established with the rapid translocation of cytosolic Nrf2 into the nucleus. In addition, transcriptional and translational upregulation of known Nrf2 regulated genes including glutamate cysteine ligase GCL , both catalytic and modulatory subunits, heme oxygenase-1, and glutathione S-transferase GST isoforms were detected. These data suggest Nrf2 activation is likely independent of classical oxidative stress or, at best, a result of a transient, low-level redox stress.

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Endothelial dysfunction is an important risk factor for cardiovascular disease, and it represents the initial step in the pathogenesis of atherosclerosis. Failure to protect against oxidative stress-induced cellular damage accounts for endothelial dysfunction in the majority of pathophysiological conditions. Nrf2, a transcription factor with a high sensitivity to oxidative stress, binds to AREs in the nucleus and promotes the transcription of a wide variety of antioxidant genes. Nrf2 is located in the cytoskeleton, adjacent to Keap1. Oxidative stress causes Nrf2 to dissociate from Keap1 and to subsequently translocate into the nucleus, which results in its binding to ARE and the transcription of downstream target genes. Experimental evidence has established that Nrf2-driven free radical detoxification pathways are important endogenous homeostatic mechanisms that are associated with vasoprotection in the setting of aging, atherosclerosis, hypertension, ischemia, and cardiovascular diseases.

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Oxidative Stress and Disease

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Joshua A. David, William J. Rifkin, Piul S. Rabbani, Daniel J.

The role of Nrf2 in oxidative stress-induced endothelial injuries

Oxidative stress resulting from environmental exposures is associated with a variety of human diseases ranging from chemical teratogenesis to cardiovascular and neurodegenerative diseases.

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