caa a22 4500 445853255 CHVBK 20180317145420.0 cr unu---uuuuu 170323e20111201xx s 000 0 eng 10.1007/s00204-011-0714-1 doi (NATIONALLICENCE)springer-10.1007/s00204-011-0714-1 Silver nanoparticles induce apoptosis and G2/M arrest via PKCζ-dependent signaling in A549 lung cells [Elektronische Daten] [Young Lee, Dong Kim, Young Lee, Jung Oh, Seokjoo Yoon, Mi Choi, Sung Lee, Ji Kim, Kyuhong Lee, Chang-Woo Song] The use of silver nanoparticles is one of the fastest growing product categories in the nanotechnology industry, with a focus on antimicrobial activity. However, thus far, toxicity data for silver nanoparticles are limited. In this study, we investigated the cytotoxic effects of silver nanoparticles (Ag NPs) and the pathway by which they affect A549 lung epithelial cells. The effects of Ag NPs on cell survival, cell cycle progression, and mRNA and protein alterations of selected cell cycle- and apoptosis-related genes were studied using formazan dye and LDH release assays, flow cytometric analysis, semi-quantitative RT-PCR, and Western blot analysis. Ag NPs reduced cell viability, increased LDH release, and modulated cell cycle distribution through the accumulation of cells at G2/M and sub-G1 phases (cell death), with a concurrent decrease in cells at G1. Ag NP treatment increased Bax and Bid mRNA levels and downregulated Bcl-2 and Bcl-w mRNAs in a dose-dependent manner. Furthermore, Ag NPs altered the mRNA levels of protein kinase C (PKC) family members. In particular, ectopic overexpression of PKCζ led to the enhancement of cellular proliferation and reduced sensitivity to Ag NPs in A549 cells. Together, these results suggest that Ag NPs induce strong toxicity and G2/M cell cycle arrest by a mechanism involving PKCζ downregulation in A549 cells. Springer-Verlag, 2011 Silver nanoparticles (Ag NPs) nationallicence G2/M arrest nationallicence Apoptosis nationallicence Protein kinase C (PKC) ζ nationallicence Lee Young Department of Anatomy, Chungnam National University, 301-040, Daejeon, Republic of Korea aut Kim Dong Department of Anatomy, Chungnam National University, 301-040, Daejeon, Republic of Korea aut Oh Jung Molecular Toxicology Team, Korea Institute of Toxicology, 305-343, Daejeon, Republic of Korea aut Yoon Seokjoo Molecular Toxicology Team, Korea Institute of Toxicology, 305-343, Daejeon, Republic of Korea aut Choi Mi Molecular Toxicology Team, Korea Institute of Toxicology, 305-343, Daejeon, Republic of Korea aut Lee Sung Environmental Toxicology Team, Korea Institute of Toxicology, 305-343, Daejeon, Republic of Korea aut Kim Ji Environmental Toxicology Team, Korea Institute of Toxicology, 305-343, Daejeon, Republic of Korea aut Lee Kyuhong Department of Inhalation Toxicology, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, 1051, Shinjeong-dong, 580-185, Jeongeup, Jeollabuk-do, Republic of Korea aut Song Chang-Woo Department of Inhalation Toxicology, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, 1051, Shinjeong-dong, 580-185, Jeongeup, Jeollabuk-do, Republic of Korea aut Archives of Toxicology Springer-Verlag 85/12(2011-12-01), 1529-1540 0340-5761 85:12<1529 2011 85 204 https://doi.org/10.1007/s00204-011-0714-1 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-011-0714-1 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lee Young Department of Anatomy, Chungnam National University, 301-040, Daejeon, Republic of Korea aut NATIONALLICENCE 700 1- Kim Dong Department of Anatomy, Chungnam National University, 301-040, Daejeon, Republic of Korea aut NATIONALLICENCE 700 1- Oh Jung Molecular Toxicology Team, Korea Institute of Toxicology, 305-343, Daejeon, Republic of Korea aut NATIONALLICENCE 700 1- Yoon Seokjoo Molecular Toxicology Team, Korea Institute of Toxicology, 305-343, Daejeon, Republic of Korea aut NATIONALLICENCE 700 1- Choi Mi Molecular Toxicology Team, Korea Institute of Toxicology, 305-343, Daejeon, Republic of Korea aut NATIONALLICENCE 700 1- Lee Sung Environmental Toxicology Team, Korea Institute of Toxicology, 305-343, Daejeon, Republic of Korea aut NATIONALLICENCE 700 1- Kim Ji Environmental Toxicology Team, Korea Institute of Toxicology, 305-343, Daejeon, Republic of Korea aut NATIONALLICENCE 700 1- Lee Kyuhong Department of Inhalation Toxicology, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, 1051, Shinjeong-dong, 580-185, Jeongeup, Jeollabuk-do, Republic of Korea aut NATIONALLICENCE 700 1- Song Chang-Woo Department of Inhalation Toxicology, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, 1051, Shinjeong-dong, 580-185, Jeongeup, Jeollabuk-do, Republic of Korea aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/12(2011-12-01), 1529-1540 0340-5761 85:12<1529 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer