title: Conservation of the Nrf2-Mediated Gene Regulation of Proteasome Subunits and Glucose Metabolism in Zebrafish.
abstract: 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, andpsmb7) and 2 enzymes involved in glucose metabolism (pgdandfbp1a) 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.
authors.affiliation: Department of Molecular and Developmental Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan; Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba 305-8575, Japan.
authors.forename: Vu Thanh
authors.identifier: 0000-0002-3458-8813
authors.initials: VT
authors.lastname: Nguyen
authors.affiliation: Department of Molecular and Developmental Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan; Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba 305-8575, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Fuse
authors.affiliation: Department of Molecular and Developmental Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan; College of Biological Sciences, University of Tsukuba, Tsukuba 305-8575, Japan.
authors.forename: Junya
authors.initials: J
authors.lastname: Tamaoki
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan; Department of Life Sciences, Graduate School of Bioresources, Mie University, Tsu 514-8507, Japan.
authors.forename: Shin-Ichi
authors.initials: SI
authors.lastname: Akiyama
authors.affiliation: Department of Genome Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Muratani
authors.affiliation: Department of Life Sciences, Graduate School of Bioresources, Mie University, Tsu 514-8507, Japan.
authors.forename: Yutaka
authors.identifier: 0000-0003-0803-4830
authors.initials: Y
authors.lastname: Tamaru
authors.affiliation: Department of Molecular and Developmental Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575, Japan.
authors.forename: Makoto
authors.identifier: 0000-0001-6660-450X
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D005947:Glucose / Q000378:metabolism*; D017403:In Situ Hybridization; D007814:Larva / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D046988:Proteasome Endopeptidase Complex / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015854:Up-Regulation; D015027:Zebrafish / Q000254:growth & development / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051267:NF-E2-Related Factor 2; D021122:Protein Subunits; D029961:Zebrafish Proteins; C495638:nfe2l2a protein, zebrafish; D046988:Proteasome Endopeptidase Complex; D005947:Glucose