Nrf2-dependent protection against acute sodium arsenite toxicity in zebrafish

Fuse, Yuji; Nguyen, Vu Tuan; Kobayashi, Makoto

doi:10.1016/j.taap.2016.06.012

Cited by 38 publications

(29 citation statements)

References 42 publications

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“…The nrf2a fh318 strain was maintained by PCR-based genotyping, as described in Fuse et al [17]. Embryos were obtained by natural mating.…”

Section: Methodsmentioning

confidence: 99%

“…We have investigated the Keap1-Nrf2 system using the zebrafish as a model and revealed that the regulation of the system is based on a similar molecular mechanism to mammals [11–15]. Moreover, an analysis of the Nrf2 mutant zebrafish strain, nrf2a fh318 , revealed that the protective role against oxidative and xenobiotic stress was conserved in the zebrafish [16, 17]. The lineup of the target genes in the zebrafish, which provides the defense function, is also being clarified from recent studies [18].…”

Section: Introductionmentioning

confidence: 99%

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Conservation of the Nrf2‐Mediated Gene Regulation of Proteasome Subunits and Glucose Metabolism in Zebrafish

Nguyen

Fuse

Tamaoki

et al. 2016

Oxidative Medicine and Cellular Longevity

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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.

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“…The nrf2a fh318 strain was maintained by PCR-based genotyping, as described in Fuse et al [17]. Embryos were obtained by natural mating.…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Conservation of the Nrf2‐Mediated Gene Regulation of Proteasome Subunits and Glucose Metabolism in Zebrafish

Nguyen

Fuse

Tamaoki

et al. 2016

Oxidative Medicine and Cellular Longevity

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“…We have been evaluating the antioxidant activity of Nrf2-activating compounds based on the improvement of the survival rate of zebrafish larvae exposed to toxic oxidative stress [15,27,28]. While the previous method of evaluation required 5 mL of compound solution for each sample (20 larvae in a 35-mm dish), it was better to reduce the volume as much as possible, since many phytochemicals are valuable and expensive.…”

Section: Establishment Of the Zebrafish-based Assay System For Evaluamentioning

confidence: 99%

“…In this study, wild-type (AB strain) and Nrf2-mutant (nfe2l2a fh318 ) [15] zebrafish larvae were used. The Nrf2-mutant line was maintained by polymerase chain reaction based genotyping, as described previously [28]. Embryos were obtained by natural mating.…”

Section: Zebrafish and Chemicalsmentioning

confidence: 99%

“…We have studied the Nrf2 pathway using zebrafish for two decades and found that the functions and regulatory mechanism of the Nrf2 pathway are highly conserved among vertebrates [17][18][19][20][21][22][23][24][25][26]. We also established a mutant line of zebrafish Nrf2 (nfe2l2a fh318 ) and demonstrated that the antioxidant activity of zebrafish larvae was increased by the treatment of sulforaphane and other Nrf2-activating compounds in an Nrf2-dependent manner [15,27,28].…”

Section: Introductionmentioning

confidence: 99%

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Evaluation of Antioxidant Activity of Spice-Derived Phytochemicals Using Zebrafish

Endo

Muraki

Fuse

2020

IJMS

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Various dietary phytochemicals seem to display antioxidant activity through the NF-E2-related factor 2 (Nrf2) pathway. However, few studies have demonstrated its antioxidant effect and Nrf2 dependency at the animal level. We constructed a zebrafish-based assay system to analyze the in vivo antioxidant activity of phytochemicals and examined the activity of 10 phytochemicals derived from spices, using this system as a pilot study. Hydrogen peroxide and arsenite were used as oxidative stressors, and Nrf2 dependency was genetically analyzed using an Nrf2-mutant zebrafish line. The activities of curcumin, diallyl trisulfide and quercetin were involved in the reduction of hydrogen peroxide toxicity, while those of cinnamaldehyde, isoeugenol and 6-(methylsulfinyl)hexyl isothiocyanate were involved in the reduction of arsenite toxicity. The antioxidant activities of these phytochemicals were all Nrf2 dependent, with the exception of cinnamaldehyde, which showed strong antioxidant effects even in Nrf2-mutant zebrafish. In summary, we succeeded in constructing an assay system to evaluate the in vivo antioxidant activity of various phytochemicals using zebrafish larvae. Using this system, we found that each spice-derived phytochemical has its own specific property and mechanism of antioxidant action.

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Gene expression analyses reveal potential mechanism of inorganic arsenic‐induced apoptosis in zebrafish

Silva,

Kudlyk,

Tryndyak

et al. 2023

J of Applied Toxicology

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Our previous study showed that sodium arsenite (200 mg/L) affected the nervous system and induced motor neuron development via the Sonic hedgehog pathway in zebrafish larvae. To gain more insight into the effects of arsenite on other signaling pathways, including apoptosis, we have performed quantitative polymerase chain reaction array‐based gene expression analyses. The 96‐well array plates contained primers for 84 genes representing 10 signaling pathways that regulate several biological functions, including apoptosis. We exposed eggs at 5 h postfertilization until the 72 h postfertilization larval stage to 200 mg/L sodium arsenite. In the Janus kinase/signal transducers and activators of transcription, nuclear factor κ‐light‐chain‐enhancer of activated B cells, and Wingless/Int‐1 signaling pathways, the expression of only one gene in each pathway was significantly altered. The expression of multiple genes was altered in the p53 and oxidative stress pathways. Sodium arsenite induced excessive apoptosis in the larvae. This compelled us to analyze specific genes in the p53 pathway, including cdkn1a, gadd45aa, and gadd45ba. Our data suggest that the p53 pathway is likely responsible for sodium arsenite‐induced apoptosis. In addition, sodium arsenite significantly reduced global DNA methylation in the zebrafish larvae, which may indicate that epigenetic factors could be dysregulated after arsenic exposure. Together, these data elucidate potential mechanisms of arsenic toxicity that could improve understanding of arsenic's effects on human health.

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Nrf2-dependent protection against acute sodium arsenite toxicity in zebrafish

Cited by 38 publications

References 42 publications

Conservation of the Nrf2‐Mediated Gene Regulation of Proteasome Subunits and Glucose Metabolism in Zebrafish

Conservation of the Nrf2‐Mediated Gene Regulation of Proteasome Subunits and Glucose Metabolism in Zebrafish

Evaluation of Antioxidant Activity of Spice-Derived Phytochemicals Using Zebrafish

Gene expression analyses reveal potential mechanism of inorganic arsenic‐induced apoptosis in zebrafish

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