Skip to main content
SpringerLink
Log in
Book cover

Molecular Toxicology in Caenorhabditis elegans pp 231–292Cite as

Functions of Protective Response-Related Signaling Pathways in the Regulation of Toxicity of Environmental Toxicants or Stresses

  • Chapter
  • First Online:

  • 288 Accesses

Abstract

In nematodes, there are many forms of protective response potentially activated by environmental toxicants or stresses. We here focused on the introduction and discussion of important protection functions of neurotransmitters, antimicrobial proteins, mitochondrial UPR, endoplasmic reticulum UPR, and autophagy for nematodes in response to environmental toxicants or stresses. The underlying molecular mechanisms for the formation of these protective responses in nematodes exposed to environmental toxicants or stresses were also carefully discussed.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   149.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Wang D-Y (2018) Nanotoxicology in Caenorhabditis elegans. Springer, Singapore

    Book  Google Scholar 

  2. Dong S-S, Qu M, Rui Q, Wang D-Y (2018) Combinational effect of titanium dioxide nanoparticles and nanopolystyrene particles at environmentally relevant concentrations on nematodes Caenorhabditis elegans. Ecotoxicol Environ Saf 161:444–450

    Article  CAS  PubMed  Google Scholar 

  3. Zhao L, Qu M, Wong G, Wang D-Y (2017) Transgenerational toxicity of nanopolystyrene particles in the range of μg/L in nematode Caenorhabditis elegans. Environ Sci Nano 4:2356–2366

    Article  CAS  Google Scholar 

  4. Qu M, Xu K-N, Li Y-H, Wong G, Wang D-Y (2018) Using acs-22 mutant Caenorhabditis elegans to detect the toxicity of nanopolystyrene particles. Sci Total Environ 643:119–126

    Article  CAS  PubMed  Google Scholar 

  5. Zhao Y-L, Wu Q-L, Li Y-P, Wang D-Y (2013) Translocation, transfer, and in vivo safety evaluation of engineered nanomaterials in the non-mammalian alternative toxicity assay model of nematode Caenorhabditis elegans. RSC Adv 3:5741–5757

    Article  CAS  Google Scholar 

  6. Ren M-X, Zhao L, Ding X-C, Krasteva N, Rui Q, Wang D-Y (2018) Developmental basis for intestinal barrier against the toxicity of graphene oxide. Part Fibre Toxicol 15:26

    Article  PubMed  PubMed Central  Google Scholar 

  7. Xiao G-S, Chen H, Krasteva N, Liu Q-Z, Wang D-Y (2018) Identification of interneurons required for the aversive response of Caenorhabditis elegans to graphene oxide. J Nanbiotechnol 16:45

    Article  Google Scholar 

  8. Ding X-C, Rui Q, Wang D-Y (2018) Functional disruption in epidermal barrier enhances toxicity and accumulation of graphene oxide. Ecotoxicol Environ Saf 163:456–464

    Article  CAS  PubMed  Google Scholar 

  9. Zhao L, Kong J-T, Krasteva N, Wang D-Y (2018) Deficit in epidermal barrier induces toxicity and translocation of PEG modified graphene oxide in nematodes. Toxicol Res 7(6):1061–1070. https://doi.org/10.1039/C8TX00136G

    Article  CAS  Google Scholar 

  10. Xiao G-S, Zhi L-T, Ding X-C, Rui Q, Wang D-Y (2017) Value of mir-247 in warning graphene oxide toxicity in nematode Caenorhabditis elegans. RSC Adv 7:52694–52701

    Article  CAS  Google Scholar 

  11. Zhao L, Wan H-X, Liu Q-Z, Wang D-Y (2017) Multi-walled carbon nanotubes-induced alterations in microRNA let-7 and its targets activate a protection mechanism by conferring a developmental timing control. Part Fibre Toxicol 14:27

    Article  PubMed  PubMed Central  Google Scholar 

  12. Wang Q-Q, Zhao S-Q, Zhao Y-L, Rui Q, Wang D-Y (2014) Toxicity and translocation of graphene oxide in Arabidopsis plants under stress conditions. RSC Adv 4:60891–60901

    Article  CAS  Google Scholar 

  13. Li Y-X, Yu S-H, Wu Q-L, Tang M, Wang D-Y (2013) Transmissions of serotonin, dopamine and glutamate are required for the formation of neurotoxicity from Al2O3-NPs in nematode Caenorhabditis elegans. Nanotoxicology 7:1004–1013

    Article  CAS  PubMed  Google Scholar 

  14. Hoshikawa H, Uno M, Honjoh S, Nishida E (2017) Octopamine enhances oxidative stress resistance through the fasting-responsive transcription factor DAF-16/FOXO in C. elegans. Genes Cells 22:210–219

    Article  CAS  PubMed  Google Scholar 

  15. Yu Y-L, Zhi L-T, Wu Q-L, Jing L-N, Wang D-Y (2018) NPR-9 regulates innate immune response in Caenorhabditis elegans by antagonizing activity of AIB interneurons. Cell Mol Immunol 15:27–37

    Article  CAS  PubMed  Google Scholar 

  16. Zhi L-T, Yu Y-L, Jiang Z-X, Wang D-Y (2017) mir-355 functions as an important link between p38 MAPK signaling and insulin signaling in the regulation of innate immunity. Sci Rep 7:14560

    Article  PubMed  PubMed Central  Google Scholar 

  17. Sun L-M, Liao K, Hong C-C, Wang D-Y (2017) Honokiol induces reactive oxygen species-mediated apoptosis in Candida albicans through mitochondrial dysfunction. PLoS One 12:e0172228

    Article  PubMed  PubMed Central  Google Scholar 

  18. Sun L-M, Liao K, Wang D-Y (2017) Honokiol induces superoxide production by targeting mitochondrial respiratory chain complex I in Candida albicans. PLoS One 12:e0184003

    Article  PubMed  PubMed Central  Google Scholar 

  19. Yu Y-L, Zhi L-T, Guan X-M, Wang D-Y, Wang D-Y (2016) FLP-4 neuropeptide and its receptor in a neuronal circuit regulate preference choice through functions of ASH-2 trithorax complex in Caenorhabditis elegans. Sci Rep 6:21485

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Sun L-M, Zhi L-T, Shakoor S, Liao K, Wang D-Y (2016) microRNAs involved in the control of innate immunity in Candida infected Caenorhabditis elegans. Sci Rep 6:36036

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sun L-M, Liao K, Li Y-P, Zhao L, Liang S, Guo D, Hu J, Wang D-Y (2016) Synergy between PVP-coated silver nanoparticles and azole antifungal against drug-resistant Candida albicans. J Nanosci Nanotechnol 16:2325–2335

    Article  CAS  PubMed  Google Scholar 

  22. Wu Q-L, Cao X-O, Yan D, Wang D-Y, Aballay A (2015) Genetic screen reveals link between maternal-effect sterile gene mes-1 and P. aeruginosa-induced neurodegeneration in C. elegans. J Biol Chem 290:29231–29239

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Xie Y, Moussaif M, Choi S, Xu L, Sze JY (2013) RFX transcription factor DAF-19 regulates 5-HT and innate immune responses to pathogenic bacteria in Caenorhabditis elegans. PLoS Genet 9:e1003324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Cao X, Aballay A (2016) Neural inhibition of dopaminergic signaling enhances immunity in a cell non-autonomous manner. Curr Biol 26:2329–2334

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Iwasaki K, Staunton J, Saifee O, Nonet ML, Thomas JH (1997) aex-3 encodes a novel regulator of presynaptic activity in C. elegans. Neuron 18:613–622

    Article  CAS  PubMed  Google Scholar 

  26. Iwasaki K, Toyonaga R (2000) The Rab3 GDP/GTP exchange factor homolog AEX-3 has a dual function in synaptic transmission. EMBO J 19:4806–4816

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Qu M, Li Y-H, Wu Q-L, Xia Y-K, Wang D-Y (2017) Neuronal ERK signaling in response to graphene oxide in nematode Caenorhabditis elegans. Nanotoxicology 11:520–533

    Article  CAS  PubMed  Google Scholar 

  28. Zhi L-T, Yu Y-L, Li X-Y, Wang D-Y, Wang D-Y (2017) Molecular control of innate immune response to Pseudomonas aeruginosa infection by intestinal let-7 in Caenorhabditis elegans. PLoS Pathog 13:e1006152

    Article  PubMed  PubMed Central  Google Scholar 

  29. Kim DH, Ewbank JJ (2018) Signaling in the innate immune response. WormBook. https://doi.org/10.1895/wormbook.1.83.2

  30. Ewbank JJ, Pujol N (2016) Local and long-range activation of innate immunity by infection and damage in C. elegans. Curr Opin Immunol 38:1–7

    Article  CAS  PubMed  Google Scholar 

  31. Kim DH (2013) Bacteria and the aging and longevity of Caenorhabditis elegans. Annu Rev Genet 47:233–246

    Article  CAS  PubMed  Google Scholar 

  32. Pukkila-Worley R, Ausubel FM (2012) Immune defense mechanisms in the Caenorhabditis elegans intestinal epithelium. Curr Opin Immunol 24:3–9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Irazoqui JE, Urbach JM, Ausubel FM (2010) Evolution of host innate defence: insights from Caenorhabditis elegans and primitive invertebrates. Nat Rev Immunol 10:47–58

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Kim DH, Ausubel FM (2005) Evolutionary perspectives on innate immunity from the study of Caenorhabditis elegans. Curr Opin Immunol 17:4–10

    Article  CAS  PubMed  Google Scholar 

  35. Ren M-X, Zhao L, Lv X, Wang D-Y (2017) Antimicrobial proteins in the response to graphene oxide in Caenorhabditis elegans. Nanotoxicology 11:578–590

    Article  CAS  PubMed  Google Scholar 

  36. Melber A, Haynes CM (2018) UPRmt regulation and output: a stress response mediated by mitochondrial-nuclear communication. Cell Res 28:281–295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Rauthan M, Pilon M (2015) A chemical screen to identify inducers of the mitochondrial unfolded protein response in C. elegans. Worm 4:e1096490

    Article  PubMed  PubMed Central  Google Scholar 

  38. Pellegrino MW, Nargund AM, Kirienko NV, Gillis R, Fiorese CJ, Haynes CM (2014) Mitochondrial UPR-regulated innate immunity provides resistance to pathogen infection. Nature 516:414–417

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Haynes CM, Yang Y, Blais SP, Neubert TA, Ron D (2010) The matrix peptide exporter HAF-1 signals a mitochondrial unfolded protein response by activating the transcription factor ZC376.7 in C. elegans. Mol Cell 37:529–540

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Nargund AM, Pellegrino MW, Fiorese CJ, Baker BM, Haynes CM (2012) Mitochondrial import efficiency of ATFS-1 regulates mitochondrial UPR activation. Science 337:587–590

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Haynes CM, Petrova K, Benedetti C, Yang Y, Ron D (2007) ClpP mediates activation of a mitochondrial unfolded protein response in C. elegans. Dev Cell 13:467–480

    Article  CAS  PubMed  Google Scholar 

  42. Rauthan M, Ranji P, Abukar R, Pilon M (2015) A mutation in Caenorhabditis elegans NDUF-7 activates the mitochondrial stress response and prolongs lifespan via ROS and CED-4. G3 5:1639–1648

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Nargund AM, Fiorese CJ, Pellegrino MW, Deng P, Haynes CM (2015) Mitochondrial and nuclear accumulation of the transcription factor ATFS-1 promotes OXPHOS recovery during the UPRmt. Mol Cell 58:123–133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Bischof LJ, Kao C-Y, Los FCO, Gonzalez MR, Shen Z, Briggs SP, van der Goot FG, Aroian RV (2008) Activation of the unfolded protein response is required for defenses against bacterial pore-forming toxin in vivo. PLoS Pathog 4:e1000176

    Article  PubMed  PubMed Central  Google Scholar 

  45. 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 

  46. Shen X, Ellis RE, Lee K, Liu C, Yang K, Solomon A, Yoshida H, Morimoto R, Kurnit DM, Mori K, Kaufman RJ (2001) Complementary signalling pathways regulate the unfolded protein response and are required for C. elegans development. Cell 107:893–903

    Article  CAS  PubMed  Google Scholar 

  47. Calfon M, Zeng H, Urano F, Till JH, Hubbard SR, Harding HP, Clark SG, Ron D (2001) IRE1 couples endoplasmic reticulum load to secretory capacity by processing the XBP-1 mRNA. Nature 415:92–96

    Article  Google Scholar 

  48. Richardson CE, Kinkel S, Kim DH (2011) Physiological IRE-1-XBP-1 and PEK-1 signaling in Caenorhabditis elegans larval development and immunity. PLoS Genet 7:e1002391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Kozlowski L, Garvis S, Bedet C, Palladino F (2014) The Caenorhabditis elegans HP1 family protein HPL-2 maintains ER homeostasis through the UPR and hormesis. Proc Natl Acad Sci U S A 111:5956–5961

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Sakaki K, Yoshina S, Shen X, Han J, DeSantis MR, Xiong M, Mitani S, Kaufman RJ (2012) RNA surveillance is required for endoplasmic reticulum homeostasis. Proc Natl Acad Sci U S A 109:8079–8084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Urano F, Calfon M, Yoneda T, Yun C, Kiraly M, Clark SG, Ron D (2002) A survival pathway for Caenorhabditis elegans with a blocked unfolded protein response. J Cell Biol 158:639–646

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Singh J, Aballay A (2017) Endoplasmic reticulum stress caused by lipoprotein accumulation suppresses immunity against bacterial pathogens and contributes to immunosenescence. MBio 8:e00778–e00717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Marza E, Taouji S, Barroso K, Raymond A, Guignard L, Bonneu M, Pallares-Lupon N, Dupuy J, Fernandez-Zapico ME, Rosenbaum J, Palladino F, Dupuy D, Chevet E (2015) Genome-wide screen identifies a novel p97/CDC-48-dependent pathway regulating ER-stress induced gene transcription. EMBO Rep 16:332–340

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Haskins KA, Russell JF, Gaddis N, Dressman HK, Aballay A (2008) Unfolded protein response genes regulated by CED-1 are required for Caenorhabditis elegans innate immunity. Dev Cell 15:87–97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. 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 

  56. Hou NS, Gutschmidt A, Choi DY, Pather K, Shi X, Watts JL, Hoppe T, Taubert S (2014) Activation of the endoplasmic reticulum unfolded protein response by lipid disequilibrium without disturbed proteostasis in vivo. Proc Natl Acad Sci U S A 111:E2271–E2280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Meléndez A, Levine B (2009) Autophagy in C. elegans. WormBook. https://doi.org/10.1895/wormbook.1.147.1

  58. Kuo C, Hansen M, Troemel E (2018) Autophagy and innate immunity: insights from invertebrate model organisms. Autophagy 14:233–242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Zou C, Ma Y, Dai L, Zhang K (2014) Autophagy protects C. elegans against necrosis during Pseudomonas aeruginosa infection. Proc Natl Acad Sci U S A 111:12480–12485

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Martinez BA, Kim H, Ray A, Caldwell GA, Caldwell KA (2015) A bacterial metabolite induces glutathione-tractable proteostatic damage, proteasomal disturbances, and PINK1-dependent autophagy in C. elegans. Cell Death Dis 6:e1908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Samokhvalov V, Scott BA, Crowder CM (2008) Autophagy protects from hypoxic injury in C. elegans. Autophagy 4:1034–1041

    Article  CAS  PubMed  Google Scholar 

  62. Visvikis O, Ihuegbu N, Labed SA, Luhachack LG, Alves AF, Wollenberg AC, Stuart LM, Stormo GD, Irazoqui JE (2014) Innate host defense requires TFEB-mediated transcription of cytoprotective and antimicrobial genes. Immunity 40:896–909

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Chen H, Kao C, Liu B, Huang S, Kuo C, Ruan J, Lin Y, Huang C, Chen Y, Wang H, Aroian RV, Chen C (2017) HLH-30/TFEB-mediated autophagy functions in a cell-autonomous manner for epithelium intrinsic cellular defense against bacterial pore-forming toxin in C. elegans. Autophagy 13:371–385

    Article  CAS  PubMed  Google Scholar 

  64. Das R, Melo JA, Thondamal M, Morton EA, Cornwell AB, Crick B, Kim JH, Swartz EW, Lamitina T, Douglas PM, Samuelsonet AV (2017) The homeodomain-interacting protein kinase HPK-1 preserves protein homeostasis and longevity through master regulatory control of the HSF-1 chaperone network and TORC1-restricted autophagy in Caenorhabditis elegans. PLoS Genet 13:e1007038

    Article  PubMed  PubMed Central  Google Scholar 

  65. Xiao Y, Liu F, Zhao P, Zou C, Zhang K (2017) PKA/KIN-1 mediates innate immune responses to bacterial pathogens in Caenorhabditis elegans. Innate Immunity 23:656–666

    Article  CAS  PubMed  Google Scholar 

  66. Kumsta C, Chang JT, Schmalz J, Hansen M (2017) Hormetic heat stress and HSF-1 induce autophagy to improve survival and proteostasis in C. elegans. Nat Commun 8:14337

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Possik E, Jalali Z, Nouet Y, Yan M, Gingras M, Schmeisser K, Panaite L, Dupuy F, Kharitidi D, Chotard L, Jones RG, Hall DH, Pause A (2014) Folliculin regulates AMPK-dependent autophagy and metabolic stress survival. PLoS Genet 10:e1004273

    Article  PubMed  PubMed Central  Google Scholar 

  68. Jia K, Thomas C, Akbar M, Sun Q, Adams-Huet B, Gilpin C, Levine B (2009) Autophagy genes protect against Salmonella typhimurium infection and mediate insulin signaling-regulated pathogen resistance. Proc Natl Acad Sci U S A 106:14564–14569

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Kirienko NV, Ausubel FM, Ruvkun G (2015) Mitophagy confers resistance to siderophore-mediated killing by Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 112:1821–1826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Li W-J, Wang D-Y, Wang D-Y (2018) Regulation of the response of Caenorhabditis elegans to simulated microgravity by p38 mitogen-activated protein kinase signaling. Sci Rep 8:857

    Article  PubMed  PubMed Central  Google Scholar 

  71. Xiao G-S, Zhao L, Huang Q, Yang J-N, Du H-H, Guo D-Q, Xia M-X, Li G-M, Chen Z-X, Wang D-Y (2018) Toxicity evaluation of Wanzhou watershed of Yangtze Three Gorges Reservoir in the flood season in Caenorhabditis elegans. Sci Rep 8:6734

    Article  PubMed  PubMed Central  Google Scholar 

  72. Yin J-C, Liu R, Jian Z-H, Yang D, Pu Y-P, Yin L-H, Wang D-Y (2018) Di (2-ethylhexyl) phthalate-induced reproductive toxicity involved in DNA damage-dependent oocyte apoptosis and oxidative stress in Caenorhabditis elegans. Ecotoxicol Environ Saf 163:298–306

    Article  CAS  PubMed  Google Scholar 

  73. Zhao L, Rui Q, Wang D-Y (2017) Molecular basis for oxidative stress induced by simulated microgravity in nematode Caenorhabditis elegans. Sci Total Environ 607–608:1381–1390

    Article  PubMed  Google Scholar 

  74. Wu Q-L, Han X-X, Wang D, Zhao F, Wang D-Y (2017) Coal combustion related fine particulate matter (PM2.5) induces toxicity in Caenorhabditis elegans by dysregulating microRNA expression. Toxicol Res 6:432–441

    Article  CAS  Google Scholar 

  75. Shao H-M, Han Z-Y, Krasteva N, Wang D-Y (2018) Identification of signaling cascade in the insulin signaling pathway in response to nanopolystyrene particles. Nanotoxicology (in press)

    Google Scholar 

  76. Xiao G-S, Zhao L, Huang Q, Du H-H, Guo D-Q, Xia M-X, Li G-M, Chen Z-X, Wang D-Y (2018) Biosafety assessment of water samples from Wanzhou watershed of Yangtze Three Gorges Reservoir in the quiet season in Caenorhabditis elegans. Sci Rep 8:14102

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. School of Medicine, Southeast University, Nanjing, China

    Dayong Wang

Authors
  1. Dayong Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Wang, D. (2019). Functions of Protective Response-Related Signaling Pathways in the Regulation of Toxicity of Environmental Toxicants or Stresses. In: Molecular Toxicology in Caenorhabditis elegans. Springer, Singapore. https://doi.org/10.1007/978-981-13-3633-1_9

Download citation

Publish with us

Policies and ethics

Search

Navigation