title: Oxidative stress, calcium homeostasis, and altered gene expression in human lung epithelial cells exposed to ZnO nanoparticles.
abstract: 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.
authors.affiliation: Department of Biological Sciences, Missouri University of Science and Technology, 105 Schrenk Hall, Rolla, MO 65409, USA.
authors.forename: Chuan-Chin
authors.initials: CC
authors.lastname: Huang
authors.forename: Robert S
authors.initials: RS
authors.lastname: Aronstam
authors.forename: Da-Ren
authors.initials: DR
authors.lastname: Chen
authors.forename: Yue-Wern
authors.initials: YW
authors.lastname: Huang
mesh_terms: 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*
chemical_list: 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