Molecular Basis for Reduced Lifespan Induced by Environmental Toxicants or Stresses

  • Dayong Wang


What’s the potential basic principle for the toxicity induction on different endpoints in nematodes exposed to environmental toxicants or stresses? To answer such a question, we here focus on the endpoint of lifespan to discuss the potential basic principle for toxicity induction from environmental toxicants or stresses. In this chapter, we will discuss how the environmental toxicants or stresses reduce lifespan by affecting the molecular basis for longevity, and how the innate immune response is involved in the regulation of longevity reduction in nematodes exposed to environmental toxicants or stresses. We will further introduce the genetic identification of genes and signaling cascade in the regulation of toxicity of environmental toxicants or stresses. We will also discuss how the environmental toxicants or stresses reduce lifespan by affecting signaling pathways associated with the stress response.


Molecular basis Lifespan reduction Environmental exposure Caenorhabditis elegans 


  1. 1.
    Zhao Y-L, Yang J-N, Wang D-Y (2016) A microRNA-mediated insulin signalling pathway regulates the toxicity of multi-walled carbon nanotubes in nematode Caenorhabditis elegans. Sci Rep 6:23234PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Wu Q-L, Zhi L-T, Qu Y-Y, Wang D-Y (2016) Quantum dots increased fat storage in intestine of Caenorhabditis elegans by influencing molecular basis for fatty acid metabolism. Nanomedicine 12:1175–1184PubMedCrossRefGoogle Scholar
  3. 3.
    Zhi L-T, Fu W, Wang X, Wang D-Y (2016) ACS-22, a protein homologous to mammalian fatty acid transport protein 4, is essential for the control of toxicity and translocation of multi-walled carbon nanotubes in Caenorhabditis elegans. RSC Adv 6:4151–4159CrossRefGoogle Scholar
  4. 4.
    Shakoor S, Sun L-M, Wang D-Y (2016) Multi-walled carbon nanotubes enhanced fungal colonization and suppressed innate immune response to fungal infection in nematodes. Toxicol Res 5:492–499CrossRefGoogle Scholar
  5. 5.
    Yang R-L, Rui Q, Kong L, Zhang N, Li Y, Wang X-Y, Tao J, Tian P-Y, Ma Y, Wei J-R, Li G-J, Wang D-Y (2016) Metallothioneins act downstream of insulin signaling to regulate toxicity of outdoor fine particulate matter (PM2.5) during Spring Festival in Beijing in nematode Caenorhabditis elegans. Toxicol Res 5:1097–1105CrossRefGoogle Scholar
  6. 6.
    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 6:432–441CrossRefGoogle Scholar
  7. 7.
    Zhi L-T, Ren M-X, Qu M, Zhang H-Y, Wang D-Y (2016) Wnt ligands differentially regulate toxicity and translocation of graphene oxide through different mechanisms in Caenorhabditis elegans. Sci Rep 6:39261PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Zhao L, Rui Q, Wang D-Y (2017) Molecular basis for oxidative stress induced by simulated microgravity in nematode Caenorhabditis elegans. Sci Total Environ 607–608:1381–1390PubMedCrossRefGoogle Scholar
  9. 9.
    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 4:2356–2366CrossRefGoogle Scholar
  10. 10.
    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 8:6734PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Chen H, Li H-R, Wang D-Y (2017) Graphene oxide dysregulates Neuroligin/NLG-1-mediated molecular signaling in interneurons in Caenorhabditis elegans. Sci Rep 7:41655PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    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 643:119–126PubMedCrossRefGoogle Scholar
  13. 13.
    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 161:444–450PubMedCrossRefGoogle Scholar
  14. 14.
    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. CrossRefGoogle Scholar
  15. 15.
    Ding X-C, Wang J, Rui Q, Wang D-Y (2018) Long-term exposure to thiolated graphene oxide in the range of μg/L induces toxicity in nematode Caenorhabditis elegans. Sci Total Environ 616–617:29–37PubMedCrossRefGoogle Scholar
  16. 16.
    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 16:45CrossRefGoogle Scholar
  17. 17.
    Wang D-Y (2018) Nanotoxicology in Caenorhabditis elegans. Springer, SingaporeCrossRefGoogle Scholar
  18. 18.
    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 8:857PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Yang R-L, Ren M-X, Rui Q, Wang D-Y (2016) A mir-231-regulated protection mechanism against the toxicity of graphene oxide in nematode Caenorhabditis elegans. Sci Rep 6:32214PubMedPubMedCentralCrossRefGoogle Scholar
  20. 20.
    Zhuang Z-H, Li M, Liu H, Luo L-B, Gu W-D, Wu Q-L, Wang D-Y (2016) Function of RSKS-1-AAK-2-DAF-16 signaling cascade in enhancing toxicity of multi-walled carbon nanotubes can be suppressed by mir-259 activation in Caenorhabditis elegans. Sci Rep 6:32409PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Johnson TE, Wood WB (1982) Genetic analysis of life-span in Caenorhabditis elegans. Proc Natl Acad Sci U S A 79:6603–6607PubMedPubMedCentralCrossRefGoogle Scholar
  22. 22.
    Klass MR (1977) Aging in the nematode Caenorhabditis elegans: major biological and environmental factors influencing life span. Mech Ageing Dev 6:413–429PubMedCrossRefGoogle Scholar
  23. 23.
    Klass MR (1983) A method for the isolation of longevity mutants in the nematode Caenorhabditis elegans and initial results. Mech Ageing Dev 22:279–286PubMedCrossRefGoogle Scholar
  24. 24.
    Kapahi P, kaeberlein M, Hansen M (2017) Dietary restriction and lifespan: lessons from invertebrate models. Ageing Res Rev 39:3–14PubMedCrossRefGoogle Scholar
  25. 25.
    Smith-Vikos T, Slack FJ (2012) MicroRNAs and their roles in aging. J Cell Sci 125:7–17PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Martins R, Lithgow GJ, Link W (2016) Long live FOXO: unraveling the role of FOXO proteins in aging and longevity. Aging Cell 15:196–207PubMedCrossRefGoogle Scholar
  27. 27.
    Hekimi A, Guarente L (2003) Genetics and the specificity of the aging process. Science 299:1351–1354PubMedCrossRefGoogle Scholar
  28. 28.
    Pan H, Finkel T (2017) Key proteins and pathways that regulate lifespan. J Biol Chem 292:6452–6460PubMedPubMedCentralCrossRefGoogle Scholar
  29. 29.
    Kenyon CJ (2010) The genetics of ageing. Nature 464:504–512PubMedCrossRefGoogle Scholar
  30. 30.
    Lapierre LR, Hansen M (2012) Lessons from C. elegans: signaling pathways for longevity. Trends Endocrinol Metab 23:637–644PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Kimura KD, Tissenbaum HA, Liu Y, Ruvkun G (1997) daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science 277:942–946PubMedCrossRefGoogle Scholar
  32. 32.
    Morris JZ, Tissenbaum HA, Ruvkun G (1996) A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature 382:536–539PubMedCrossRefGoogle Scholar
  33. 33.
    Hertweck M, Gobel C, Baumeister R (2004) C. elegans SGK-1 is the critical component in the Akt/PKB kinase complex to control stress response and life span. Dev Cell 6:577–588PubMedCrossRefGoogle Scholar
  34. 34.
    Paradis S, Ruvkun G (1998) Caenorhabditis elegans Akt/PKB transduces insulin receptor-like signals from AGE-1 PI3 kinase to the DAF-16 transcription factor. Genes Dev 12:2488–2498PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Paradis S, Ailion M, Toker A, Thomas JH, Ruvkun G (1999) A PDK1 homolog is necessary and sufficient to transduce AGE-1 PI3 kinase signals that regulate diapause in Caenorhabditis elegans. Genes Dev 13:1438–1452PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Henderson ST, Johnson TE (2001) daf-16 integrates developmental and environmental inputs to mediate aging in the nematode Caenorhabditis elegans. Curr Biol 11:1975–1980PubMedCrossRefGoogle Scholar
  37. 37.
    Lee RY, Hench J, Ruvkun G (2001) Regulation of C. elegans DAF-16 and its human ortholog FKHRL1 by the daf-2 insulin-like signaling pathway. Curr Biol 11:1950–1957PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Lin K, Hsin H, Libina N, Kenyon C (2001) Regulation of the Caenorhabditis elegans longevity protein DAF-16 by insulin/IGF-1 and germline signaling. Nat Genet 28:139–145PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Lin K, Dorman JB, Rodan A, Kenyon C (1997) daf-16: an HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science 278:1319–1322PubMedCrossRefGoogle Scholar
  40. 40.
    Ogg S, Paradis S, Gottlieb S, Patterson GI, Lee L, Tissenbaum HA, Ruvkun G (1997) The Fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature 389:994–999PubMedCrossRefGoogle Scholar
  41. 41.
    Dorman JB, Albinder B, Shroyer T, Kenyon C (1995) The age-1 and daf-2 genes function in a common pathway to control the lifespan of Caenorhabditis elegans. Genetics 141:1399–1406PubMedPubMedCentralGoogle Scholar
  42. 42.
    Zhao Y-L, Yang R-L, Rui Q, Wang D-Y (2016) Intestinal insulin signaling encodes two different molecular mechanisms for the shortened longevity induced by graphene oxide in Caenorhabditis elegans. Sci Rep 6:24024PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Boehm M, Slack F (2005) A developmental timing microRNA and its target regulate life span in C. elegans. Science 310:1954–1957PubMedCrossRefGoogle Scholar
  44. 44.
    Hsu AL, Murphy CT, Kenyon C (2003) Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 300:1142–1145PubMedCrossRefGoogle Scholar
  45. 45.
    Tissenbaum HA, Guarente L (2001) Increased dosage of a sir-2 gene extends lifespan in Caenorhabditis elegans. Nature 410:227–230PubMedCrossRefGoogle Scholar
  46. 46.
    Wolff S, Ma H, Burch D, Maciel GA, Hunter T, Dillin A (2006) SMK-1, an essential regulator of DAF-16-mediated longevity. Cell 124:1039–1053PubMedCrossRefGoogle Scholar
  47. 47.
    Shore DE, Ruvkun G (2013) A cytoprotective perspective on longevity regulation. Trends Cell Biol 23:409–420PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Honda Y, Honda S (1999) The daf-2 gene network for longevity regulates oxidative stress resistance and Mn-superoxide dismutase gene expression in Caenorhabditis elegans. FASEB J 13:1385–1478PubMedCrossRefGoogle Scholar
  49. 49.
    Cherkasova V, Ayyadevara S, Egilmez N, Shmookler Reis R (2000) Diverse Caenorhabditis elegans genes that are upregulated in dauer larvae also show elevated transcript levels in long-lived, aged, or starved adults. J Mol Biol 300:433–481PubMedCrossRefGoogle Scholar
  50. 50.
    Yu H, Larsen P (2001) DAF-16-dependent and independent expression targets of DAF-2 insulin receptor-like pathway in Caenorhabditis elegans include FKBPs. J Mol Biol 314:1017–1045PubMedCrossRefGoogle Scholar
  51. 51.
    Halaschek-Wiener J, Khattra JS, McKay S, Pouzyrev A, Stott JM, Yang GS, Holt RA, Jones SJ, Marra MA, Brooks-Wilson AR, Riddle DL (2005) Analysis of long-lived C. elegans daf-2 mutants using serial analysis of gene expression. Genome Res 15:603–615PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Murphy C, McCarroll SA, Bargmann CI, Fraser A, Kamath RS, Ahringer J, Li H, Kenyon C (2003) Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424:277–360PubMedCrossRefGoogle Scholar
  53. 53.
    Lakowski B, Hekimi S (1998) The genetics of caloric restriction in Caenorhabditis elegans. Proc Natl Acad Sci U S A 95:13091–13096PubMedPubMedCentralCrossRefGoogle Scholar
  54. 54.
    Jia K, Chen D, Riddle DL (2004) The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span. Development 131:3897–3906PubMedCrossRefGoogle Scholar
  55. 55.
    Vellai T, Takacs-Vellai K, Zhang Y, Kovacs AL, Orosz L, Muller F (2003) Genetics: influence of TOR kinase on lifespan in C. elegans. Nature 426:620PubMedCrossRefGoogle Scholar
  56. 56.
    Gelino S, Chang JT, Kumsta C, She X, Davis A, Nguyen C, Panowski S, Hansen M (2016) Intestinal autophagy improves healthspan and longevity in C. elegans during dietary restriction. PLoS Genet 12:e1006135PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Toth ML, Sigmond T, Borsos E, Barna J, Erdelyi P, Takacs-Vellai K, Orosz L, Kovacs AL, Csikos G, Sass M, Vellai T (2008) Longevity pathways converge on autophagy genes to regulate life span in Caenorhabditis elegans. Autophagy 4:330–338PubMedCrossRefGoogle Scholar
  58. 58.
    Jia K, Levine B (2007) Autophagy is required for dietary restriction-mediated lifespan extension in C. elegans. Autophagy 3:597–599PubMedCrossRefGoogle Scholar
  59. 59.
    Hansen M, Chandra A, Mitic LL, Onken B, Driscoll M, Kenyon C (2008) A role for autophagy in the extension of lifespan by dietary restriction in C. elegans. PLoS Genet 4:e24PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Heestand BN, Shen Y, Liu W, Magner DB, Storm N, Meharg C, Habermann B, Antebi A (2013) Dietary restriction induced longevity is mediated by nuclear receptor NHR-62 in Caenorhabditis elegans. PLoS Genet 9:e1003651PubMedPubMedCentralCrossRefGoogle Scholar
  61. 61.
    Lapierre LR, De Magalhaes Filho CD, McQuary PR, Chu CC, Visvikis O, Chang JT, Gelino S, Ong B, Davis AE, Irazoqui JE, Dillin A, Hansen M (2013) The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in Caenorhabditis elegans. Nat Commun 4:2267PubMedCrossRefGoogle Scholar
  62. 62.
    Dillin A, Hsu AL, Arantes-Oliveira N, Lehrer-Graiwer J, Hsin H, Fraser AG, Kamath RS, Ahringer J, Kenyon C (2002) Rates of behavior and aging specified by mitochondrial function during development. Science 298:2398–2401PubMedCrossRefGoogle Scholar
  63. 63.
    Feng J, Bussiere F, Hekimi S (2001) Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans. Dev Cell 1:633–644PubMedCrossRefGoogle Scholar
  64. 64.
    Lee SS, Lee RY, Fraser AG, Kamath RS, Ahringer J, Ruvkun G (2003) A systematic RNAi screen identifies a critical role for mitochondria in C. elegans longevity. Nat Genet 33:40–48PubMedCrossRefGoogle Scholar
  65. 65.
    Hartman PS, Ishii N, Kayser EB, Morgan PG, Sedensky MM (2001) Mitochondrial mutations differentially affect aging, mutability and anesthetic sensitivity in Caenorhabditis elegans. Mech Ageing Dev 122:1187–1201PubMedCrossRefGoogle Scholar
  66. 66.
    Kayser EB, Sedensky MM, Morgan PG (2004) The effects of complex I function and oxidative damage on lifespan and anesthetic sensitivity in Caenorhabditis elegans. Mech Ageing Dev 125:455–464PubMedCrossRefGoogle Scholar
  67. 67.
    Tsang WY, Sayles LC, Grad LI, Pilgrim DB, Lemire BD (2001) Mitochondrial respiratory chain deficiency in Caenorhabditis elegans results in developmental arrest and increased life span. J Biol Chem 276:32240–32246PubMedCrossRefGoogle Scholar
  68. 68.
    Yang W, Hekimi S (2010) Two modes of mitochondrial dysfunction lead independently to lifespan extension in Caenorhabditis elegans. Aging Cell 9:433–447PubMedCrossRefGoogle Scholar
  69. 69.
    Ishii N, Fujii M, Hartman PS, Tsuda M, Yasuda K, Senoo-Matsuda N, Yanase S, Ayusawa D, Suzuki K (1998) A mutation in succinate dehydrogenase cytochrome b causes oxidative stress and ageing in nematodes. Nature 394:694–697PubMedCrossRefGoogle Scholar
  70. 70.
    Ishii N, Takahashi K, Tomita S, Keino T, Honda S, Yoshino K, Suzuki K (1990) A methyl viologen-sensitive mutant of the nematode Caenorhabditis elegans. Mutat Res 237:165–171PubMedCrossRefGoogle Scholar
  71. 71.
    Hosokawa H, Ishii N, Ishida H, Ichimori K, Nakazawa H, Suzuki K (1994) Rapid accumulation of fluorescent material with aging in an oxygen-sensitive mutant mev-1 of Caenorhabditis elegans. Mech Ageing Dev 74:161–170PubMedCrossRefGoogle Scholar
  72. 72.
    Senoo-Matsuda N, Yasuda K, Tsuda M, Ohkubo T, Yoshimura S, Nakazawa H, Hartman PS, Ishii N (2001) A defect in the cytochrome b large subunit in complex II causes both superoxide anion overproduction and abnormal energy metabolism in Caenorhabditis elegans. J Biol Chem 276:41553–41558PubMedCrossRefGoogle Scholar
  73. 73.
    Hamilton B, Dong Y, Shindo M, Liu W, Odell I, Ruvkun G, Lee SS (2005) A systematic RNAi screen for longevity genes in C. elegans. Genes Dev 19:1544–1555PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Wong A, Boutis P, Hekimi S (1995) Mutations in the clk-1 gene of Caenorhabditis elegans affect developmental and behavioral timing. Genetics 139:1247–1259PubMedPubMedCentralGoogle Scholar
  75. 75.
    Van Raamsdonk JM, Hekimi S (2009) Deletion of the mitochondrial superoxide dismutase sod-2 extends lifespan in Caenorhabditis elegans. PLoS Genet 5:e1000361PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Dancy BM, Sedensky MM, Morgan PG (2014) Effects of the mitochondrial respiratory chain on longevity in C. elegans. Exp Gerontol 56:245–255PubMedCrossRefGoogle Scholar
  77. 77.
    Antebi A (2013) Regulation of longevity by the reproductive system. Exp Gerontol 28:596–602CrossRefGoogle Scholar
  78. 78.
    Hsin H, Kenyon C (1999) Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399:362–366PubMedCrossRefGoogle Scholar
  79. 79.
    Goudeau J, Bellemin S, Toselli-Mollereau E, Shamalnasab M, Chen Y, Aguilaniu H (2011) Fatty acid desaturation links germ cell loss to longevity through NHR-80/HNF4 in C. elegans. PLoS Biol 9:e1000599PubMedPubMedCentralCrossRefGoogle Scholar
  80. 80.
    Arantes-Oliveira N, Berman JR, Kenyon C (2003) Healthy animals with extreme longevity. Science 302:611PubMedCrossRefGoogle Scholar
  81. 81.
    Larsen PL, Albert PS, Riddle DL (1995) Genes that regulate both development and longevity in Caenorhabditis elegans. Genetics 139:1567–1583PubMedPubMedCentralGoogle Scholar
  82. 82.
    Wolff S, Dillin A (2006) The trifecta of aging in Caenorhabditis elegans. Exp Gerontol 41:894–903PubMedCrossRefGoogle Scholar
  83. 83.
    Chan TY (1999) Health hazards due to clenbuterol residues in food. J Toxicol Clin Toxicol 37:517–519PubMedCrossRefGoogle Scholar
  84. 84.
    Yen M, Ewald MB (2012) Toxicity of weight loss agents. J Med Toxicol 8:145–152PubMedPubMedCentralCrossRefGoogle Scholar
  85. 85.
    Yaeger MJ, Mullin K, Ensley SM, Ware WA, Slavin RE (2012) Myocardial toxicity in a group of greyhounds administered ractopamine. Vet Pathol 49:569–573PubMedCrossRefGoogle Scholar
  86. 86.
    Zhuang Z, Zhao Y, Wu Q, Li M, Liu H, Sun L, Gao W, Wang D (2014) Adverse effects from clenbuterol and ractopamine on nematode Caenorhabditis elegans and the underlying mechanism. PLoS ONE 9:e85482PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Shi X, Gong H, Li Y, Wang C, Cheng L, Liu Z (2013) Graphene-based magnetic plasmonic nanocomposite for dual imaging and photothermal therapy. Biomaterials 34:4786–4793PubMedCrossRefGoogle Scholar
  88. 88.
    Park S, Ruoff RS (2009) Chemical methods for the production of graphenes. Nat Nanotechnol 4:217–224PubMedCrossRefGoogle Scholar
  89. 89.
    Yang K, Li Y, Tan X, Peng R, Liu Z (2013) Behavior and toxicity of graphene and its functionalized derivatives in biological systems. Small 9:1492–1503PubMedCrossRefGoogle Scholar
  90. 90.
    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. Particle Fibre Toxicol 15:26CrossRefGoogle Scholar
  91. 91.
    Ren M-X, Zhao L, Lv X, Wang D-Y (2017) Antimicrobial proteins in the response to graphene oxide in Caenorhabditis elegans. Nanotoxicology 11:578–590PubMedCrossRefGoogle Scholar
  92. 92.
    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 7:52694–52701CrossRefGoogle Scholar
  93. 93.
    Wu Q-L, Zhao Y-L, Zhao G, Wang D-Y (2014) microRNAs control of in vivo toxicity from graphene oxide in Caenorhabditis elegans. Nanomedicine 10:1401–1410PubMedCrossRefGoogle Scholar
  94. 94.
    Wu Q-L, Yin L, Li X, Tang M, Zhang T, Wang D-Y (2013) Contributions of altered permeability of intestinal barrier and defecation behavior to toxicity formation from graphene oxide in nematode Caenorhabditis elegans. Nanoscale 5:9934–9943PubMedCrossRefGoogle Scholar
  95. 95.
    Wu Q-L, Zhao Y-L, Fang J-P, Wang D-Y (2014) Immune response is required for the control of in vivo translocation and chronic toxicity of graphene oxide. Nanoscale 6:5894–5906PubMedCrossRefGoogle Scholar
  96. 96.
    Hahm J, Kim S, Paik Y (2011) GPA-9 is a novel regulator of innate immunity against Escherichia coli foods in adult Caenorhabditis elegans. Aging Cell 10:208–219PubMedCrossRefGoogle Scholar
  97. 97.
    Kawli T, Tan M (2008) Neuroendocrine signals modulate the innate immunity of Caenorhabditis elegans through insulin signalling. Nat Immunol 9:1415–1424PubMedCrossRefGoogle Scholar
  98. 98.
    Pukkila-Worley R, Ausubel FM (2012) Immune defense mechanisms in the Caenorhabditis elegans intestinal epithelium. Curr Opin Immunol 24:3–9PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Black HS (1987) Potential involvement of free radical reactions in ultraviolet light-mediated cutaneous damage. Photochem Photobiol 46:213–221PubMedCrossRefGoogle Scholar
  100. 100.
    Friedberg EC (1985) DNA repair. W.H. Freeman and Company, New YorkGoogle Scholar
  101. 101.
    Murakami S, Johnson TE (1996) A genetic pathway conferring life extension and resistance by UV stress in Caenorhabditis elegans. Genetics 143:1207–1218PubMedPubMedCentralGoogle Scholar
  102. 102.
    Hayakawa T, Kato K, Jayakawa R, Hisamoto N, Katsumoto K, Takeda K, Ichijo H (2011) Regulation of anoxic death in Caenorhabditis elegans by mammalian apoptosis signal-regulating kinase (ASK) family proteins. Genetics 187:785–792PubMedPubMedCentralCrossRefGoogle Scholar
  103. 103.
    Kim DH, Ausubel FM (2005) Evolutionary perspectives on innate immunity from the study of Caenorhabditis elegans. Curr Opin Immunol 17:4–10PubMedCrossRefGoogle Scholar
  104. 104.
    Zhao Y-L, Zhi L-T, Wu Q-L, Yu Y-L, Sun Q-Q, Wang D-Y (2016) p38 MAPK-SKN-1/Nrf signaling cascade is required for intestinal barrier against graphene oxide toxicity in Caenorhabditis elegans. Nanotoxicology 10:1469–1479PubMedCrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Dayong Wang
    • 1
  1. 1.School of MedicineSoutheast UniversityNanjingChina

Personalised recommendations