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

Nivedita Chatterjee, Hyun Jeong Eom, Jinhee Choi

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

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.

Original languageEnglish
Pages (from-to)122-133
Number of pages12
JournalEnvironmental and Molecular Mutagenesis
Volume55
Issue number2
DOIs
StatePublished - Mar 2014

Keywords

  • 8-oxo-GTPases
  • 8OHdG
  • DNA glycosylases
  • P38 MAPK
  • PMK-1
  • Silver nanoparticles

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