Role of Nrf2 in Oxidative Stress and Toxicity

Abstract

Organismal life encounters reactive oxidants from internal metabolism and environmental toxicant exposure. Reactive oxygen and nitrogen species cause oxidative stress and are traditionally viewed as being harmful. On the other hand, controlled production of oxidants in normal cells serves useful purposes to regulate signaling pathways. Reactive oxidants are counterbalanced by complex antioxidant defense systems regulated by a web of pathways to ensure that the response to oxidants is adequate for the body's needs. A recurrent theme in oxidant signaling and antioxidant defense is reactive cysteine thiol-based redox signaling. The nuclear factor erythroid 2-related factor 2 (Nrf2) is an emerging regulator of cellular resistance to oxidants. Nrf2 controls the basal and induced expression of an array of antioxidant response element-dependent genes to regulate the physiological and pathophysiological outcomes of oxidant exposure. This review discusses the impact of Nrf2 on oxidative stress and toxicity and how Nrf2 senses oxidants and regulates antioxidant defense.

An Important Function of Petrosiol E in Inducing the Differentiation of Neuronal Progenitors and in Protecting Them against Oxidative Stress

“…Nrf2 is a master transcription factor in protecting cells from oxidative stress by orchestrating the expression of oxidative stress‐related genes 25. Importantly, previous studies also demonstrated that Nrf2 is indispensable for neuronal differentiation 26.…”

Transcription factor NFE2L2/NRF2 modulates chaperone-mediated autophagy through the regulation of LAMP2A

“…Knockout of Lamp2a or Nfe2l2 makes cells more susceptible to different stressors [8,32], indicating a crucial role in the maintenance of cell homeostasis under different circumstances. In fact, previous work supports the notion that redox status tightly controls CMA activity, presumably to eliminate proteins oxidized during mild oxidative damage [14].…”

Dietary phenylalanine-improved intestinal barrier health in young grass carp (Ctenopharyngodon idella) is associated with increased immune status and regulated gene expression of cytokines, tight junction proteins, antioxidant enzymes and related signalling molecules

“…Lambertucci et al [80] reported that the changes in antioxidant enzyme activities were associated with antioxidant enzyme gene transcription in rat. In fish, Nrf2 has been demonstrated as a critical transcription factor that promotes the transcription of antioxidant enzyme genes by binding to the antioxidant response element in the promoter region of these antioxidant enzyme genes [81]. Thus, in order to further elucidate the underlying mechanism by which dietary Phe enhances the antioxidant capacity to protect intestinal integrity in fish, we next investigated the effect of Phe on the gene expression of antioxidant enzymes and signal molecules Nrf2 and Keap1 in the intestines of young grass carp.…”