关键词: Nrf2; Keap1; ARE; 信号通路; 氧化应激

Abstract: Oxidative stress is a malignant state characterized by redox imbalance, which is one of the important factor leading to tissue damage and disease. Oxidative stress is known to be closely associated with reproductive disturbance, decreased disease resistance, and reduced production performance and product quality of livestock and poultry. Nuclear factor erythroid 2 related factor (Nrf2)/Kelch-like ECH-associated protein 1 (Keap1)-antioxidant response element (ARE) signaling pathway is one of the most important defense mechanism against oxidative stress. It maintains intracellular redox equilibrium, metabolism and protein homeostasis, and exerts biological functions such as anti-inflammation, anti-cancer and anti-aging by regulating the transcription of multiple downstream cytoprotective genes. Under normal physiological conditions, Nrf2, a transcription factor with a high sensitivity to oxidative stress, is negatively regulated by Keap1, which targets Nrf2 for ubiquitination and degradation by the ubiquitin proteasome system. Oxidative stress causes Nrf2 to dissociate from Keap1 and to subsequently translocate into the nucleus, which interacts with small Maf (sMaf) to form heterodimer and binds to ARE, leading to increased transcription of antioxidant genes. The Nrf2 regulatory network is complex, and its activity is subjected to the regulation at various levels, including transcription and post-transcription, protein stability, subcellular localization, and post-translation modification. The author introduces the molecular structural basis of Nrf2/Keap1-ARE signaling pathway, its biological functions and the current knowledge of its activity regulation, in order to acquire a greater depth of understanding Nrf2 regulatory mechanism and provide a theoretical basis for improving the health of livestock and devising Nrf2-based strategies for disease intervention.

Key words: Nrf2; Keap1; ARE; signaling pathway; oxidative stress