a Department of Chemical and Biological Work Environment , National Institute of Occupational Health , Oslo , Norway.
b Max Planck Institute for Cell Biology and Genetics , Dresden , Germany.
Nanotoxicology. 2018 Mar;12(2):138-152. doi: 10.1080/17435390.2018.1425500. Epub 2018 Jan 19.
The effects of long-term chronic exposure of human lung cells to multi-walled carbon nanotubes (MWCNT) and their impact upon cellular proteins and lipids were investigated. Since the lung is the major target organ, an in vitro normal bronchial epithelial cell line model was used. Additionally, to better mimic exposure to manufactured nanomaterials at occupational settings, cells were continuously exposed to two non-toxic and low doses of a MWCNT for 13-weeks. MWCNT-treatment increased ROS levels in cells without increasing oxidative DNA damage and resulted in differential expression of multiple anti- and pro-apoptotic proteins. The proteomic analysis of the MWCNT-exposed cells showed that among more than 5000 identified proteins; more than 200 were differentially expressed in the treated cells. Functional analyses revealed association of these differentially regulated proteins to cellular processes such as cell death and survival, cellular assembly, and organization. Similarly, shotgun lipidomic profiling revealed accumulation of multiple lipid classes. Our results indicate that long-term MWCNT-exposure of human normal lung cells at occupationally relevant low-doses may alter both the proteome and the lipidome profiles of the target epithelial cells in the lung.
研究了长期慢性暴露于多壁碳纳米管 (MWCNT) 对人肺细胞的影响及其对细胞蛋白质和脂质的影响。由于肺是主要的靶器官,因此使用了体外正常支气管上皮细胞系模型。此外,为了更好地模拟职业环境中制造的纳米材料的暴露,细胞连续 13 周暴露于两种无毒和低剂量的 MWCNT 下。MWCNT 处理增加了细胞中的 ROS 水平,而不会增加氧化 DNA 损伤,并导致多种抗凋亡和促凋亡蛋白的差异表达。MWCNT 暴露细胞的蛋白质组学分析表明,在鉴定出的 5000 多种蛋白质中;在处理过的细胞中有 200 多种表达不同。功能分析表明,这些差异调节的蛋白质与细胞死亡和存活、细胞组装和组织等细胞过程有关。同样, shotgun 脂质组学分析显示多种脂质类别的积累。我们的研究结果表明,长期职业相关低剂量 MWCNT 暴露于人正常肺细胞可能会改变肺上皮细胞的蛋白质组和脂质组谱。