PMID- 30842368 OWN - NLM STAT- MEDLINE DCOM- 20190328 LR - 20190328 IS - 1880-3989 (Electronic) IS - 0388-1350 (Linking) VI - 44 IP - 3 DP - 2019 TI - Mechanisms of silver nanoparticles-induced cytotoxicity and apoptosis in rat tracheal epithelial cells. PG - 155-165 LID - 10.2131/jts.44.155 [doi] AB - Silver nanoparticles (AgNPs) are increasingly utilized in a number of applications. This study was designed to investigate AgNPs induced cytotoxicity, oxidative stress and apoptosis in rat tracheal epithelial cells (RTE). The RTE cells were treated with 0, 100 mug/L and 10,000 mug/L of the AgNPs with diameters of 10 nm and 100 nm for 12 hr. The cell inhibition level, apoptosis ratio, reactive oxygen species (ROS), malondialdehyde (MDA) and metallothionein (MT) content were determined. The mRNA expression of cytoc, caspase 3, and caspase 9 was measured by quantitative real-time polymerase chain reaction (qRT-PCR). In addition, we also analyzed the cytoc, caspase 3, pro-caspase 3, caspase 9, and pro-caspase 9 protein expression by western blotting. Electric cell-substrate impedance sensing (ECIS) analysis showed that the growth and proliferation of RTE cells were significantly inhibited in a dose-dependent manner under AgNPs exposure. The cell dynamic changes induced by 10 nm AgNPs were more severe than that of the 100 nm AgNPs exposure group. The intracellular MT, ROS, and MDA content increased when the exposure concentration increased and size reduced, whereas Ca(2+)-ATPase activity and Na(+)/K(+)-ATPase activity changed inversely. The relative expression of protein of cytoc, caspase 3, and caspase 9 were upregulated significantly, which indicated that AgNPs induced apoptosis of RTE cells through the caspase-dependent mitochondrial pathway. Our results demonstrate that AgNPs caused obvious cytotoxicity, oxidative stress, and apoptosis in RTE cells, which promoted the releasing of cytochrome C and pro-apoptotic proteins into the cytoplasm to activate the caspase cascade and finally led to apoptosis. FAU - Tang, Juan AU - Tang J AD - College of Life and Environmental Sciences, Hangzhou Normal University, China. FAU - Lu, Xiangjun AU - Lu X AD - College of Life and Environmental Sciences, Hangzhou Normal University, China. FAU - Chen, Bin AU - Chen B AD - College of Life and Environmental Sciences, Hangzhou Normal University, China. FAU - Cai, Enqi AU - Cai E AD - College of Life and Environmental Sciences, Hangzhou Normal University, China. FAU - Liu, Wenli AU - Liu W AD - College of Life and Environmental Sciences, Hangzhou Normal University, China. FAU - Jiang, Jinxiao AU - Jiang J AD - College of Life and Environmental Sciences, Hangzhou Normal University, China. FAU - Chen, Feifei AU - Chen F AD - College of Life and Environmental Sciences, Hangzhou Normal University, China. FAU - Shan, Xiaodong AU - Shan X AD - College of Life and Environmental Sciences, Hangzhou Normal University, China. FAU - Zhang, Hangjun AU - Zhang H AD - College of Life and Environmental Sciences, Hangzhou Normal University, China. AD - Key Laboratory of Hangzhou City for Ecosystem Protection and Restoration, Hangzhou Normal University, China. LA - eng PT - Journal Article PL - Japan TA - J Toxicol Sci JT - The Journal of toxicological sciences JID - 7805798 RN - 0 (Cation Transport Proteins) RN - 0 (Reactive Oxygen Species) RN - 3M4G523W1G (Silver) RN - 4Y8F71G49Q (Malondialdehyde) RN - EC 3.4.22.- (Casp3 protein, rat) RN - EC 3.4.22.- (Casp9 protein, rat) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.22.- (Caspase 9) SB - IM MH - Animals MH - Apoptosis/drug effects MH - Caspase 3/genetics/metabolism MH - Caspase 9/genetics/metabolism MH - Cation Transport Proteins/metabolism MH - Cell Line MH - Epithelial Cells/*drug effects/metabolism MH - Malondialdehyde/metabolism MH - Metal Nanoparticles/*toxicity MH - Oxidative Stress/drug effects MH - Rats MH - Reactive Oxygen Species/metabolism MH - Silver/*toxicity MH - Trachea/cytology OTO - NOTNLM OT - Apoptosis OT - Cytotoxicity OT - Oxidative stress OT - Rat tracheal epithelial cells OT - Silver nanoparticles EDAT- 2019/03/08 06:00 MHDA- 2019/03/29 06:00 CRDT- 2019/03/08 06:00 PHST- 2019/03/08 06:00 [entrez] PHST- 2019/03/08 06:00 [pubmed] PHST- 2019/03/29 06:00 [medline] AID - 10.2131/jts.44.155 [doi] PST - ppublish SO - J Toxicol Sci. 2019;44(3):155-165. doi: 10.2131/jts.44.155.