title: Effects of silver nanoparticles on oxidative DNA damage-repair as a function of p38 MAPK status: a comparative approach using human Jurkat T cells and the nematode Caenorhabditis elegans.
abstract: The large-scale use of silver nanoparticles (AgNPs) has raised concerns over potential impacts on the environment and human health. We previously reported that AgNP exposure causes an increase in reactive oxygen species, DNA damage, and induction of p38 MAPK and PMK-1 in Jurkat T cells and in Caenorhabditis elegans. To elucidate the underlying mechanisms of AgNP toxicity, here we evaluate the effects of AgNPs on oxidative DNA damage-repair (in human and C. elegans DNA glycosylases hOGG1, hNTH1, NTH-1, and 8-oxo-GTPases-hMTH1, NDX-4) and explore the role of p38 MAPK and PMK-1 in this process. Our comparative approach examined viability, gene expression, and enzyme activities in wild type (WT) and p38 MAPK knock-down (KD) Jurkat T cells (in vitro) and in WT and pmk-1 loss-of-function mutant strains of C. elegans (in vivo). The results suggest that p38 MAPK/PMK-1 plays protective role against AgNP-mediated toxicity, reduced viability and greater accumulation of 8OHdG was observed in AgNP-treated KD cells, and in pmk-1 mutant worms compared with their WT counterparts, respectively. Furthermore, dose-dependent alterations in hOGG1, hMTH1, and NDX-4 expression and enzyme activity, and survival in ndx-4 mutant worms occurred following AgNP exposure. Interestingly, the absence or depletion of p38 MAPK/PMK-1 caused impaired and additive effects in AgNP-induced ndx-4(ok1003); pmk-1(RNAi) mutant survival, and hOGG1 and NDX-4 expression and enzyme activity, which may lead to higher accumulation of 8OHdG. Together, the results indicate that p38 MAPK/PMK-1 plays an important protective role in AgNP-induced oxidative DNA damage-repair which is conserved from C. elegans to humans.
authors.affiliation: School of Environmental Engineering, Graduate School of Energy and Environmental system Engineering, University of Seoul, 163 Siripdaero, Dongdaemun-gu, Seoul, 130-743, Korea.
authors.forename: Nivedita
authors.initials: N
authors.lastname: Chatterjee
authors.forename: Hyun Jeong
authors.initials: HJ
authors.lastname: Eom
authors.forename: Jinhee
authors.initials: J
authors.lastname: Choi
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D017173:Caenorhabditis elegans / Q000201:enzymology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism / Q000502:physiology; D002470:Cell Survival; D004249:DNA Damage; D045647:DNA Glycosylases / Q000378:metabolism; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism; D043224:Deoxyribonuclease (Pyrimidine Dimer) / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D019169:Jurkat Cells; D053768:Metal Nanoparticles / Q000633:toxicity*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D012834:Silver / Q000633:toxicity*; D048051:p38 Mitogen-Activated Protein Kinases / Q000502:physiology*
chemical_list: D000890:Anti-Infective Agents; D029742:Caenorhabditis elegans Proteins; D012834:Silver; D020928:Mitogen-Activated Protein Kinases; C463460:Pmk-1 protein, C elegans; D048051:p38 Mitogen-Activated Protein Kinases; D043224:Deoxyribonuclease (Pyrimidine Dimer); C468347:NTHL1 protein, human; D010744:Phosphoric Monoester Hydrolases; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; C557890:NDX-4 protein, C elegans; C078207:8-oxodGTPase; D045643:DNA Repair Enzymes
keywords: 8-oxo-GTPases; 8OHdG; DNA glycosylases; PMK-1; p38 MAPK; silver nanoparticles