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Knock-down of transcription factor skinhead-1 exacerbates arsenite-induced oxidative damage in Caenorhabditis elegans

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Abstract

Transcription factor, skinhead-1 (skn-1) has been demonstrated to play central roles in regulation of oxidative damage. Arsenite is an oxidative damage inducer in the environment. However, the role of skn-1 in arsenite-induced oxidative damage remains unclear. Thus, in this study, by using RNAi feeding, different toxic responses of wild-type and skn-1 knockdown nematodes to arsenite were evaluated. Our results demonstrated that arsenite did not show any significant impacts on locomotory behaviors, but skn-1 knock-down worms were much more sensitive to arsenite treatment, manifested by an aggravated reduction of survival rate than that of wild-type nematodes. In arsenite-treated worms, down-regulation of skn-1 significantly exacerbated the arsenite-induced changed expressions of oxidative damage-related genes, xbp-1, apl-1 and trxr-2, but these regulated effects of skn-1 were not observed on spr-4 and sel-12 expressions under arsenite treatment. These findings together suggest that skn-1 may play a vital role in protection of C. elegans from arsenite-induced oxidative damage.

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Data Availability

All the original data are available upon reasonable request for correspondence authors.

References

  • Abdul KSM, Jayasinghe SS, Chandana EP, Jayasumana C, De Silva PMC (2015) Arsenic and human health effects: a review. Environ Toxicol Pharmacol 40:828–846

    Article  PubMed  Google Scholar 

  • Blackwell TK, Steinbaugh MJ, Hourihan JM, Ewald CY, Isik M (2015) SKN-1/Nrf, stress responses, and aging in Caenorhabditis elegans. Free Radic Biol Med 88:290–301

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bornhorst J et al (2020) Toxicity of three types of arsenolipids: species-specific effects in Caenorhabditis elegans. Mettalomics 12:794–798

    Article  CAS  Google Scholar 

  • Cacho-Valadez B et al (2012) The characterization of the Caenorhabditis elegans mitochondrial thioredoxin system uncovers an unexpected protective role of thioredoxin reductase 2 in β-amyloid peptide toxicity. Antioxidants Redox Signal 16:1384–1400

    Article  CAS  Google Scholar 

  • Chalfie M, Sulston J (1981) Developmental genetics of the mechanosensory neurons of Caenorhabditis elegans. Dev Biol 82:358–370

    Article  CAS  PubMed  Google Scholar 

  • Escudero-Lourdes C (2016) Toxicity mechanisms of arsenic that are shared with neurodegenerative diseases and cognitive impairment: role of oxidative stress and inflammatory responses. Neurotoxicology 53:223–235

    Article  CAS  PubMed  Google Scholar 

  • Ewald CY, Li C (2012) Caenorhabditis elegans as a model organism to study APP function. Exp Brain Res 217:397–411

    Article  CAS  PubMed  Google Scholar 

  • Ewald CY, Raps DA, Li C (2012) APL-1, the Alzheimer’s Amyloid precursor protein in Caenorhabditis elegans, modulates multiple metabolic pathways throughout development. Genetics 191:493–507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Flora SJ (2011) Arsenic-induced oxidative stress and its reversibility. Free Radical Biol Med 51:257–281

    Article  CAS  Google Scholar 

  • Gems D, Doonan R (2008) Oxidative Stress and Aging in the NematodeCaenorhabditis elegans. In: Oxidative Stress in Aging. Springer, pp 81–110

  • Glover-Cutter KM, Lin S, Blackwell TK (2013) Integration of the unfolded protein and oxidative stress responses through SKN-1/Nrf. PLoS Genet 9:e1003701

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grau-Perez M et al (2018) Arsenic exposure, diabetes-related genes and diabetes prevalence in a general population from Spain. Environ Pollut 235:948–955

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He J, Charlet L (2013) A review of arsenic presence in China drinking water. J Hydrol 492:79–88

    Article  CAS  Google Scholar 

  • Hu Y et al (2018) The PKCδ-Nrf2-ARE signalling pathway may be involved in oxidative stress in arsenic-induced liver damage in rats. Environ Toxicol Pharmacol 62:79–87

    Article  CAS  PubMed  Google Scholar 

  • Jiang Y, Chen J, Wu Y, Wang Q, Li H (2016) Sublethal toxicity endpoints of heavy metals to the nematode Caenorhabditis elegans. PLoS ONE 11:e0148014

    Article  PubMed  PubMed Central  Google Scholar 

  • Jomova K et al (2011) Arsenic: toxicity, oxidative stress and human disease. J Appl Toxicol 31:95–107

    CAS  PubMed  Google Scholar 

  • Li H et al. (2019) Arginine methylation of SKN-1 promotes oxidative stress resistance in Caenorhabditis elegans. Redox Biolo 101111

  • Liao VH-C, Yu C-W (2005) Caenorhabditis elegans gcs-1 confers resistance to arsenic-induced oxidative stress. Biometals 18:519–528

    Article  CAS  PubMed  Google Scholar 

  • Loboda A, Damulewicz M, Pyza E, Jozkowicz A, Dulak J (2016) Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism. Cell Mol Life Sci 73:3221–3247

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lu T et al (2014) REST and stress resistance in ageing and Alzheimer’s disease. Nature 507:448

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nagashima T, Oami E, Kutsuna N, Ishiura S, Suo S (2016) Dopamine regulates body size in Caenorhabditis elegans. Dev Biol 412:128–138

    Article  CAS  PubMed  Google Scholar 

  • Naujokas MF, Anderson B, Ahsan H, Aposhian HV, Graziano JH, Thompson C, Suk WA (2013) The broad scope of health effects from chronic arsenic exposure: update on a worldwide public health problem. Environ Health Perspect 121:295–302

    Article  PubMed  PubMed Central  Google Scholar 

  • Oberoi S, Devleesschauwer B, Gibb HJ, Barchowsky A (2019) Global burden of cancer and coronary heart disease resulting from dietary exposure to arsenic, 2015 Environmental research

  • Papp D, Csermely P, Sőti C (2012) A role for SKN-1/Nrf in pathogen resistance and immunosenescence in Caenorhabditis elegans. PLoS Pathog 8:e1002673

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park SK, Tedesco PM, Johnson TE (2009) Oxidative stress and longevity in Caenorhabditis elegans as mediated by SKN-1. Aging Cell 8:258–269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Park H-EH, Jung Y, Lee S-JV (2017) Survival assays using Caenorhabditis elegans. Mol Cells 40:90

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prakash C, Kumar VJC (2016) Arsenic-induced mitochondrial oxidative damage is mediated by decreased PGC-1α expression and its downstream targets in rat brain. Chem Biol Interact 256:228–235

    Article  CAS  PubMed  Google Scholar 

  • Roh JY, Lee J, Choi J (2006) Assessment of stress-related gene expression in the heavy metal-exposed nematode Caenorhabditis elegans: a potential biomarker for metal-induced toxicity monitoring and environmental risk assessment. Environ Toxicol Chem 25:2946–2956

    Article  CAS  PubMed  Google Scholar 

  • Ryoo I-g, Kwak M-K (2018) Regulatory crosstalk between the oxidative stress-related transcription factor Nfe2l2/Nrf2 and mitochondria. Toxicol Appl Pharmacol 359:24–33

    Article  CAS  PubMed  Google Scholar 

  • Sanchez TR, Powers M, Perzanowski M, George CM, Graziano JH, Navas-Acien A (2018) A meta-analysis of arsenic exposure and lung function: is there evidence of restrictive or obstructive lung disease? Curr Environ Health Rep 5:244–254

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sarasija S, Norman KR (2015) A γ-secretase independent role for presenilin in calcium homeostasis impacts mitochondrial function and morphology in Caenorhabditis elegans. Genetics 201:1453–1466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Taylor RC, Dillin A (2013) XBP-1 is a cell-nonautonomous regulator of stress resistance and longevity. Cell 153:1435–1447

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang D, Xing X (2008) Assessment of locomotion behavioral defects induced by acute toxicity from heavy metal exposure in nematode Caenorhabditis elegans. J Environ Sci 20:1132–1137

    Article  CAS  Google Scholar 

  • Wang S, Zhao Y, Wu L, Tang M, Su C, Hei TK, Yu Z (2007) Induction of germline cell cycle arrest and apoptosis by sodium arsenite in Caenorhabditis elegans. Chem Res Toxicol 20:181–186

    Article  CAS  PubMed  Google Scholar 

  • Xu M, Niu Q, Hu Y, Feng G, Wang H, Li SJOm, longevity c (2019) Proanthocyanidins antagonize arsenic-induced oxidative damage and promote arsenic methylation through activation of the Nrf2 signaling pathway 2019

  • Yu C-W, Liao VH-CJEs, Technology (2016) Transgenerational reproductive effects of arsenite are associated with H3K4 dimethylation and SPR-5 downregulation in Caenorhabditis elegans. Environ Sci Technol 50:10673–10681

    Article  CAS  PubMed  Google Scholar 

  • Yu C-W, How CM, Liao VH-C (2016) Arsenite exposure accelerates aging process regulated by the transcription factor DAF-16/FOXO in Caenorhabditis elegans. Chemosphere 150:632–638

    Article  CAS  PubMed  Google Scholar 

  • Zhang X et al (2020) Arsenic induces transgenerational behavior disorders in Caenorhabditis elegans and its underlying mechanisms. Chemosphere 252:126510

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

This research was supported by College Students Scientific Research and Innovation Experimental Project of Chongqing Medical University (Grant Number: 201746 and LTMCMTS201806). Natural Science Foundation of Fujian Province (Grant Number: 2018J05149).

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Author notes

  1. Yijie Mao and Ling Yao have contributed equally.

Authors and Affiliations

  1. Department of Occupational and Environmental Health, School of Public Health and Management, Chongqing Medical University, Chongqing, People’s Republic of China

    Yijie Mao & Chengzhi Chen

  2. Department of Orthopedics, The Affiliated Hospital of Putian University, Fujian, People’s Republic of China

    Ling Yao

  3. Center of Experimental Teaching for Public Health, Experimental Teaching and Management Center, Chongqing Medical University, Chongqing, People’s Republic of China

    Xuejun Jiang

  4. Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China

    Golamaully Sumayyah

  5. Institute of Life Sciences, Chongqing Medical University, Chongqing, People’s Republic of China

    Zhen Zou

  6. Dongsheng Lung-Brain Disease Joint Lab, Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Zhen Zou & Chengzhi Chen

  7. Laboratory Animal Center, Chongqing Medical University, Yuzhong District, Address: No. 1, Yixueyuan Road, Chongqing, 400016, People’s Republic of China

    Qiying Yi

Authors
  1. Yijie Mao
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  2. Ling Yao
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Contributions

YM and YL performed the major experiments. ZZ provided the advice on the study design and helped in the data analysis. YL, GS and XJ revised the manuscript. CC and YQ conceived this project, designed the experiments, overseen the progress of work, wrote and corrected the manuscript with inputs from all authors.

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Correspondence to Qiying Yi or Chengzhi Chen.

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Mao, Y., Yao, L., Jiang, X. et al. Knock-down of transcription factor skinhead-1 exacerbates arsenite-induced oxidative damage in Caenorhabditis elegans. Biometals 34, 675–686 (2021). https://doi.org/10.1007/s10534-021-00303-2

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  • DOI: https://doi.org/10.1007/s10534-021-00303-2

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