Proteomic analysis of cellular response induced by multi-walled carbon nanotubes exposure in A549 cells.
The wide application of multi-walled carbon nanotubes (MWCNT) has raised serious concerns about their safety on human health and the environment. However, the potential harmful effects of MWCNT remain unclear and contradictory. To clarify the potentially toxic effects of MWCNT and to elucidate the associated underlying mechanisms, the effects of MWCNT on human lung adenocarcinoma A549 cells were examined at both the cellular and the protein level. Cytotoxicity and genotoxicity were examined, followed by a proteomic analysis (2-DE coupled with LC-MS/MS) of the cellular response to MWCNT. Our results demonstrate that MWCNT induces cytotoxicity in A549 cells only at relatively high concentrations and longer exposure time. Within a relatively low dosage range (30 µg/ml) and short time period (24 h), MWCNT treatment does not induce significant cytotoxicity, cell cycle changes, apoptosis, or DNA damage. However, at these low doses and times, MWCNT treatment causes significant changes in protein expression. A total of 106 proteins show altered expression at various time points and dosages, and of these, 52 proteins were further identified by MS. Identified proteins are involved in several cellular processes including proliferation, stress, and cellular skeleton organization. In particular, MWCNT treatment causes increases in actin expression. This increase has the potential to contribute to increased migration capacity and may be mediated by reactive oxygen species (ROS).
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Infectious Diseases Diagnosis and Therapy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China ; Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, China ; Zhejiang Academy of Medical Sciences, Hangzhou, China.
Li
L
Ju
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Infectious Diseases Diagnosis and Therapy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China ; Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, China.
Guanglin
G
Zhang
Zhejiang Academy of Medical Sciences, Hangzhou, China.
Xing
X
Zhang
Zhejiang Academy of Medical Sciences, Hangzhou, China.
Zhenyu
Z
Jia
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Infectious Diseases Diagnosis and Therapy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China ; Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, China.
Xiangjing
X
Gao
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Infectious Diseases Diagnosis and Therapy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China ; Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, China.
Ying
Y
Jiang
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Infectious Diseases Diagnosis and Therapy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China ; Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, China.
Chunlan
C
Yan
Department of Basic Science, Division of Biochemistry, Loma Linda University School of Medicine, Loma Linda, California, United States of America.
Penelope J
PJ
Duerksen-Hughes
Life Science Division, Lawrence Berkeley National Laboratory, Berkeley, California, United States of America.
Fanqing Frank
FF
Chen
Hangzhou Normal University School of Public Health, Hangzhou, China.
Hongjuan
H
Li
Department of Toxicology, Zhejiang University School of Public Health, Hangzhou, China.
Xinqiang
X
Zhu
Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Infectious Diseases Diagnosis and Therapy, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China ; College of Biotechnology, Zhejiang Agriculture and Forestry University, Hangzhou, China.
Jun
J
Yang
D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D006801:Humans; D037742:Nanotubes, Carbon / Q000633:toxicity*; D040901:Proteomics; D017382:Reactive Oxygen Species / Q000378:metabolism; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D016207:Cytokines; D037742:Nanotubes, Carbon; D017382:Reactive Oxygen Species