Upregulating Nrf2-dependent antioxidant defenses in Pacific oysters Crassostrea gigas: Investigating the Nrf2/Keap1 pathway in bivalves

Abstract

Analysis of the Pacific oyster Crassostrea gigas annotated genome revealed genes with conserved sequences belonging to typical cap 'n' collar Nrf2 domain, a major player in antioxidant protection, and domains belonging to Nrf2 cytoplasmic repressor (Keap1), but little is known about Nrf2/Keap1 induction in bivalves. C. gigas were exposed to waterborne 10 and 30μM curcumin, a known inducer of the mammalian Nrf2. Curcumin disappeared from the seawater after 10h, and accumulated in the gills (10h) and digestive gland (10-96h). A clear induction of glutathione (GSH)-related antioxidant defenses was observed at 96h in the gills of curcumin exposed animals (10 and 30μM), including GSH levels, and the activity of glutathione reductase (GR), glutathione peroxidase (GPx), and glutathione S-transferase (GST). This response was completely absent in the digestive gland, in line with the idea that bivalve gills act as a major site for antioxidant protection under acute exposure. The relative mRNA levels coding glutamate-cysteine ligase, GR, GPx2 and GSTpi were clearly induced by curcumin treatment (30μM, 24h). Curcumin pre-treatment for 96h increased oyster resistance to cumene hydroperoxide, but neither Nrf2 nor Keap1 genes were modulated by curcumin. However, the conserved sequences belonging to typical Nrf2 and Keap1 domains, and the notorious induction of antioxidant defense-related genes known to be controlled by Nrf2 in mammals, indicates a functional Nrf2/Keap1 pathway in bivalves, and curcumin seems to be a new tool to investigate the antioxidant response in bivalves.

Effects of dietary lysine levels on growth performance and antioxidative capacity in channel catfish Ictalurus punctatus

“…Nuclear factor erythroid 2‐related factor 2 (Nrf2) is a critical transcription factor in cellular oxidative stress response (Hui & Yang, 2018). Kelch‐like ECH‐associated protein 1 (Keap1) senses oxidative stress and affects the Nrf2 mRNA expression (Danielli et al, 2017). Keap1‐Nrf2 pathway plays an essential role in activating antioxidative genes (Wang et al, 2019).…”

Effects of dietary lipid levels on growth performance, hepatic health, lipid metabolism and intestinal microbiota on Trachinotus ovatus

“…However, when the cells are exposed to ROS or electrophile, Nrf2 dissociates from Keap1 and rapidly translocates into the nucleus, and then form a heterodimer with the small Maf protein, which ultimately bind to antioxidant response element (ARE) (Heiss et al, 2013;Ho et al, 2012). Nrf2-Keap1 pathway controls the expression of antioxidant gene include HO-1 (Klaassen & Reisman, 2010), SOD (Zhu et al, 2005(Zhu et al, , 2008, CAT (Zhu et al, 2008), glutathione peroxidase (GPx) (Naidu et al, 2015) and GR (Danielli et al, 2017). In this study, the Nrf2-Keap1 pathway was used to evaluate the effects of different lipid levels on the antioxidant capacity of T. ovatus.…”

Effects of calcium dobesilate on Nrf2, Keap1 and HO-1 in the lenses of D-galactose-induced cataracts in rats

“…However, when the cells are exposed to a hyperoxic environment, the conformation of Keap1 protein changes, preventing it from binding to Nrf2. Nrf2 is then released into the nucleus, expressed extensively, and promotes the expression of downstream antioxidant HO-1, imparting resistance to oxidative damage ( 14 ). Research has further shown that the expression levels of Nrf2, Keap1 and HO-1 are all decreased in the lenses of cataract patients, which indicates that the mechanism of the signaling pathway for antioxidant protection is damaged.…”