In the present study, the involvement of oxidative stress, as a toxic mechanism of silver nanoparticles (AgNPs), was investigated in Caenorhabditis elegans, focusing on the p38
mitogen-activated protein kinase (MAPK) pathway. Initially, AgNPs was tested as a potential oxidative stress inducer in C. elegans and; subsequently, the potential upstream signaling pathway activated in response to AgNPs exposure was investigated, paying special attention to the AgNPs-induced alteration in the C. elegans p38
signaling pathway. The expressions of the downstream genes, known to be regulated by the p38
-MAPK, such as glutathione S- transferases (GSTs), and the p38
dependent transcription factors (TFs) were also investigated in wildtype (N2) and pmk-1
) mutant C. elegans exposed to AgNPs. The overall results indicated that AgNPs exposure lead increased reactive oxygen species (ROS) formation, PMK-1, GST and HIF-1 activations and reproduction failure in wildtype (N2) C. elegans; whereas, none of these phenomena were observed in the pmk-1
) mutant. These results suggest that oxidative stress is an important toxic mechanism of AgNPs in C. elegans and that PMK-1 plays an important role in the response to oxidative stress induced by AgNPs. The results also suggest that GST is a PMK-1 dependent down-stream effecter protein and hypoxia-inducible factor (HIF-1) is a PMK-1 dependent TF on AgNPs exposure in C. elegans, which both play an important role in the PMK-1 mediated defense pathway to AgNPs exposure. Acknowledgements : This work was supported by National Research Foundation of Korea (NRF) grant (2010-0016195). Keywords: silver nanoparticles; Caenorhabditis elegans; oxidative stress; PMK-1; GST; HIF-1.