title: Silver nanoparticles down-regulate Nrf2-mediated 8-oxoguanine DNA glycosylase 1 through inactivation of extracellular regulated kinase and protein kinase B in human Chang liver cells.
abstract: Recently, we reported that silver nanoparticles (AgNPs) induced reactive oxygen species (ROS) generation and the resultant oxidative stress contributes to the cell damage associated with AgNPs. 8-Oxoguanine (8-oxoG) is sensitive marker of ROS-induced DNA damage. 8-Oxoguanine DNA glycosylase 1 (OGG1) is an important DNA repair enzyme that recognizes and excises 8-oxoG. The aim of the present study was to examine the effect of AgNPs-induced oxidative stress on OGG1 and to elucidate mechanisms underlying AgNPs toxicity. AgNPs decreased OGG1 mRNA and protein expression, resulting in decreased OGG1 activity. Decreased OGG1 activity in AgNPs-treated cells led to increased 8-oxoG levels. The transcription factor NF-E2-related factor 2 (Nrf2) is an important factor in the inducible regulation of OGG1. AgNPs treatment decreased nuclear Nrf2 expression, translocation into nucleus, and transcriptional activity of Nrf2. Extracellular regulated kinase (ERK) and protein kinase B (PKB, AKT), which are upstream of Nrf2, contribute to OGG1 expression. AgNPs attenuated both active forms of ERK and AKT protein expression, resulting in suppression of Nrf2 and decrease of OGG1 expression. These studies demonstrate that down-regulation of Nrf2-mediated OGG1 in exposure to AgNPs occurs through ERK and AKT inactivation.
authors.affiliation: School of Medicine and Applied Radiological Science Research Institute, Jeju National University, Jeju, Republic of Korea.
authors.forename: Mei Jing
authors.initials: MJ
authors.lastname: Piao
authors.forename: Ki Cheon
authors.initials: KC
authors.lastname: Kim
authors.forename: Jeong-Yun
authors.initials: JY
authors.lastname: Choi
authors.forename: Jinhee
authors.initials: J
authors.lastname: Choi
authors.forename: Jin Won
authors.initials: JW
authors.lastname: Hyun
mesh_terms: D015153:Blotting, Western; D002460:Cell Line; D045647:DNA Glycosylases / Q000037:antagonists & inhibitors*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors*; D006801:Humans; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D053768:Metal Nanoparticles / Q000633:toxicity*; D051267:NF-E2-Related Factor 2 / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018030:Silver Compounds / Q000494:pharmacology*
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D017382:Reactive Oxygen Species; D018030:Silver Compounds; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human