title: Toxicological effects of multi-walled carbon nanotubes on Saccharomyces cerevisiae: The uptake kinetics and mechanisms and the toxic responses.
abstract: Using Saccharomyces cerevisiae as an experimental model, the potential toxicological effects of oxidized multi-walled carbon nanotubes (MWCNTs) were investigated following exposure to 0-600mg/L for 24h. Results indicated that MWCNTs (>100mg/L) had adverse effects on the cell proliferation. MWCNTs were clearly visible in lysosome, vacuole, endosome, mitochondria, multivesicular body and localization in the perinuclear region. The uptake kinetics data demonstrated that the maximum MWCNTs content (209.61mg/g) was reached at 3h, and a steady state was reached after 18h. Based on the combined results of transmission electron microscope, endocytosis inhibition experiments and endocytosis-related genes (END3, END6, Sla2 and Rsp5) expression analysis, we elucidated MWCNTs uptake mechanism: (i) via a direct penetration of single MWCNTs; (ii) via endocytosis of single MWCNTs; and (iii) via endocytosis of MWCNTs aggregates. The percentage of apoptosis was significant increased at 600mg/L. The decrease of mitochondrial transmembrane potential and the leakage of cytochrome c shown dose-dependent manners. Interestingly, there was no significant increase of reactive oxygen species (ROS). The apoptosis-related genes (SOD1, SOD2, Yca1, Nma111 and Nuc1) were significant changed. These results obtained in our study demonstrated that oxidized MWCNTs induce Saccharomyces cerevisiae apoptosis via mitochondrial impairment pathway.
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
authors.forename: Song
authors.initials: S
authors.lastname: Zhu
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Zhu
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China.
authors.forename: Aiguo
authors.initials: A
authors.lastname: Huang
authors.affiliation: College of Science, Northwest A&F University, Yangling 712100, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Hu
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China. Electronic address: wanggaoxue@126.com.
authors.forename: Gaoxue
authors.initials: G
authors.lastname: Wang
authors.affiliation: College of Animal Science and Technology, Northwest A&F University, Yangling 712100, China. Electronic address: feiling@nwsuaf.edu.cn.
authors.forename: Fei
authors.initials: F
authors.lastname: Ling
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis / Q000187:drug effects; D007700:Kinetics; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D037742:Nanotubes, Carbon / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure
chemical_list: D051017:Apoptosis Regulatory Proteins; D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species; D045304:Cytochromes c
keywords: Carbon nanotube; Mitochondrial impairment; Toxicological effect; Uptake; Yeast