Oxidative stress and apoptosis induced by titanium dioxide nanoparticles in cultured BEAS-2B cells.
As the applications of industrial nanoparticles are being developed, the concerns on the environmental health are increasing. Cytotoxicities of titanium dioxide nanoparticles of different concentrations (5, 10, 20 and 40 microg/ml) were evaluated in this study using a cultured human bronchial epithelial cell line, BEAS-2B. Exposure of the cultured cells to nanoparticles led to cell death, reactive oxygen species (ROS) increase, reduced glutathione (GSH) decrease, and the induction of oxidative stress-related genes such as heme oxygenase-1, thioredoxin reductase, glutathione-S-transferase, catalase, and a hypoxia inducible gene. The ROS increase by titanium dioxide nanoparticles triggered the activation of cytosolic caspase-3 and chromatin condensation, which means that titanium dioxide nanoparticles exert cytotoxicity by an apoptotic process. Furthermore, the expressions of inflammation-related genes such as interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), TNF-a, and C-X-C motif ligand 2 (CXCL2) were also elevated. The induction of IL-8 by titanium dioxide nanoparticles was inhibited by the pre-treatment with SB203580 and PD98059, which means that the IL-8 was induced through p38 mitogen-activated protein kinase (MAPK) pathway and/or extracellular signal (ERK) pathway. Uptake of the nanoparticles into the cultured cells was observed and titanium dioxide nanoparticles seemed to penetrate into the cytoplasm and locate in the peri-region of the nucleus as aggregated particles, which may induce direct interactions between the particles and cellular molecules, to cause adverse biological responses.
Park
Eun-Jung
EJ
College of Pharmacy, Dongduk Women's University, 23-1, Wolgok-dong, Seongbuk-gu, Seoul 136-714, Republic of Korea.
Yi
Jongheop
J
Chung
Kyu-Hyuck
KH
Ryu
Doug-Young
DY
Choi
Jinhee
J
Park
Kwangsik
K
D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002875:Chromosomes / Q000187:drug effects / Q000648:ultrastructure; D005456:Fluorescent Dyes; D015870:Gene Expression / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007211:Indoles; D053758:Nanoparticles / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014025:Titanium / Q000633:toxicity*
D005456:Fluorescent Dyes; D007211:Indoles; D017382:Reactive Oxygen Species; C009495:titanium dioxide; C007293:DAPI; D014025:Titanium; D053148:Caspase 3; D005978:Glutathione