ZFIN ID: ZDB-PUB-170125-8
Conservation of the Nrf2-Mediated Gene Regulation of Proteasome Subunits and Glucose Metabolism in Zebrafish
Nguyen, V.T., Fuse, Y., Tamaoki, J., Akiyama, S.I., Muratani, M., Tamaru, Y., Kobayashi, M.
Date: 2016
Source: Oxidative medicine and cellular longevity   2016: 5720574 (Journal)
Registered Authors: Fuse, Yuji, Kobayashi, Makoto, Nguyen, Vu Thanh, Tamaoki, Junya, Tamaru, Yutaka
Keywords: none
Microarrays: GEO:GSE86174
MeSH Terms:
  • Animals
  • Gene Expression Regulation
  • Glucose/metabolism*
  • In Situ Hybridization
  • Larva/metabolism
  • Liver/metabolism
  • NF-E2-Related Factor 2/genetics
  • NF-E2-Related Factor 2/metabolism*
  • Oligonucleotide Array Sequence Analysis
  • Proteasome Endopeptidase Complex/genetics
  • Proteasome Endopeptidase Complex/metabolism*
  • Protein Subunits/genetics
  • Protein Subunits/metabolism
  • Real-Time Polymerase Chain Reaction
  • Up-Regulation
  • Zebrafish/growth & development
  • Zebrafish/metabolism
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 28116036 Full text @ Oxid Med Cell Longev
The Keap1-Nrf2 system is an evolutionarily conserved defense mechanism against oxidative and xenobiotic stress. Besides the exogenous stress response, Nrf2 has been found to regulate numerous cellular functions, including protein turnover and glucose metabolism; however, the evolutionary origins of these functions remain unknown. In the present study, we searched for novel target genes associated with the zebrafish Nrf2 to answer this question. A microarray analysis of zebrafish embryos that overexpressed Nrf2 revealed that 115 candidate genes were targets of Nrf2, including genes encoding proteasome subunits and enzymes involved in glucose metabolism. A real-time quantitative PCR suggested that the expression of 3 proteasome subunits (psma3, psma5, and psmb7) and 2 enzymes involved in glucose metabolism (pgd and fbp1a) were regulated by zebrafish Nrf2. We thus next examined the upregulation of these genes by an Nrf2 activator, diethyl maleate, using Nrf2 mutant zebrafish larvae. The results of real-time quantitative PCR and whole-mount in situ hybridization showed that all of these 5 genes were upregulated by diethyl maleate treatment in an Nrf2-dependent manner, especially in the liver. These findings implied that the Nrf2-mediated regulation of the proteasome subunits and glucose metabolism is evolutionarily conserved among vertebrates.