Host: The Japanese Society of Toxicology
Name : The 49th Annual Meeting of the Japanese Society of Toxicology
Date : June 30, 2022 - July 02, 2022
Silver nanoparticles (AgNPs) act on the endoplasmic reticulum (ER) stress /autophagy, and led to cell death. However, the mechanism has not been clarified. In the present study, molecular basis of the ER stress/autophagy and Rubicon were investigated by using neuroblastoma SH-SY5Y cells following exposure to AgNPs. AgNPs were treated with 0-100μg Ag/mL and 10μM salubrinal, which causes sustained phosphorylation of eIF2α, for 24 hours. Cell death was assessed by MTT assay. Lysosomes and autophagosomes were labeled by LysoTracker and DAPRed and observed by a confocal laser scanning microscope. Quantification of ER stress/autophagy related factors were evaluated by western blotting and q-PCR. Cell death was induced by AgNPs dose dependent manner, significantly further induced with salubrinal. The number of autophagosomes, phosphorylated eIF2α, GRP78,CHOP, p62, LC3B-II were increased by AgNPs and salubrinal. The combined use of AgNPs and salubrinal leads to suppress Rubicon. These results were suggested that AgNPs induced CHOP expressions and impaired autophagic flow, but salubrinal activated ER stress/autophagy, resulting in excessive CHOP expression and autophagosomal accumulation, led to cell death. This study may contribute to elucidate the mechanism of AgNPs induced cell death via ER stress/autophagy and Rubicon.
