ZFIN ID: ZDB-PUB-121205-45
Role of Nrf2 antioxidant defense in mitigating cadmium-induced oxidative stress in the olfactory system of zebrafish
Wang, L., and Gallagher, E.P.
Date: 2013
Source: Toxicology and applied pharmacology   266(2): 177-186 (Journal)
Registered Authors: Gallagher, Evan P., Wang, Lu
Keywords: Nrf2, cadmium, oxidative stress, zebrafish, olfactory injury
MeSH Terms:
  • Animals
  • Antioxidants/metabolism*
  • Cadmium/toxicity*
  • Dose-Response Relationship, Drug
  • Embryo, Nonmammalian/drug effects
  • Embryo, Nonmammalian/metabolism
  • Gene Expression Regulation, Developmental/drug effects
  • Gene Knockdown Techniques
  • Isothiocyanates
  • NF-E2-Related Factor 2/metabolism*
  • Olfactory Pathways/drug effects*
  • Oxidative Stress/drug effects*
  • Thiocyanates/pharmacology
  • Time Factors
  • Zebrafish
  • Zebrafish Proteins/metabolism*
PubMed: 23174481 Full text @ Tox. App. Pharmacol.
ABSTRACT

Exposure to trace metals can disrupt olfactory function in fish leading to a loss of behaviors critical to survival. Cadmium (Cd) is an olfactory toxicant that elicits cellular oxidative stress as a mechanism of toxicity while also inducing protective cellular antioxidant genes via activation of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) pathway. However, the molecular mechanisms of Cd-induced olfactory injury have not been characterized. In the present study, we investigated the role of the Nrf2-mediated antioxidant defense pathway in protecting against Cd-induced olfactory injury in zebrafish. A dose-dependent induction of Nrf2-regulated antioxidant genes associated with cellular responses to oxidative stress was observed in the olfactory system of adult zebrafish following 24 h Cd exposure. Zebrafish larvae exposed to Cd for 3 h showed increased glutathione S-transferase pi (gst pi), glutamate–cysteine ligase catalytic subunit (gclc), heme oxygenase 1 (hmox1) and peroxiredoxin 1 (prdx1) mRNA levels indicative of Nrf2 activation, and which were blocked by morpholino-mediated Nrf2 knockdown. The inhibition of antioxidant gene induction in Cd-exposed Nrf2 morphants was associated with disruption of olfactory driven behaviors, increased cell death and loss of olfactory sensory neurons (OSNs). Nrf2 morphants also exhibited a downregulation of OSN-specific genes after Cd exposure. Pre-incubation of embryos with sulforaphane (SFN) partially protected against Cd-induced olfactory tissue damage. Collectively, our results indicate that oxidative stress is an important mechanism of Cd-mediated injury in the zebrafish olfactory system. Moreover, the Nrf2 pathway plays a protective role against cellular oxidative damage and is important in maintaining zebrafish olfactory function.

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