Oxidative stress, calcium homeostasis, and altered gene expression in human lung epithelial cells exposed to ZnO nanoparticles.
The influence of 20nm ZnO nanoparticles on cytotoxicity, oxidative stress, intracellular calcium homeostasis, and gene expression was studied in human bronchial epithelial cells (BEAS-2B). ZnO caused a concentration- and time-dependent cytotoxicity while elevating oxidative stress and causing membrane damage (cellular LDH release). There was a remarkably steep relationship between concentration and toxicity at concentrations from 5 to 10microg/ml. Cytotoxicity was completely abolished by the antioxidant N-acetylcysteine (NAC). Exposure to ZnO also increased intracellular calcium levels ([Ca(2+)](in)) in a concentration- and time-dependent manner that was partially attenuated by NAC. Nifedipine, a calcium channel blocker, partially attenuated the elevated [Ca(2+)](in), indicating that some of the excess [Ca(2+)](in) is a result of influx from outside the cell. The relationships between oxidative stress, [Ca(2+)](in), and cytotoxicity are discussed. Exposure to a sublethal concentration of ZnO increased the expression of four genes that are involved in apoptosis and oxidative stress responses BNIP, PRDX3, PRNP, and TXRND1, by at least 2.5-fold. Thus, ZnO alters transcriptional regulation in BEAS-2B cells.
Huang
Chuan-Chin
CC
Department of Biological Sciences, Missouri University of Science and Technology, 105 Schrenk Hall, Rolla, MO 65409, USA.
Aronstam
Robert S
RS
Chen
Da-Ren
DR
Huang
Yue-Wern
YW
D000111:Acetylcysteine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D053758:Nanoparticles / Q000633:toxicity*; D009543:Nifedipine / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015034:Zinc Oxide / Q000633:toxicity*
D002121:Calcium Channel Blockers; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D007770:L-Lactate Dehydrogenase; D009543:Nifedipine; D015034:Zinc Oxide; D002118:Calcium; D000111:Acetylcysteine