| Graphene quantum dots in alveolar macrophage: uptake-exocytosis, accumulation in nuclei, nuclear responses and DNA cleavage | |
Xu, Lina; Dai, Yanhui; Wang, Zhenyu; Zhao, Jian; Li, Fei ; White, Jason C.; Xing, Baoshan
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| 发表期刊 | PARTICLE AND FIBRE TOXICOLOGY
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| ISSN | 1743-8977 |
| 2018-11-13 | |
| 卷号 | 15页码:45 |
| 关键词 | Aminated graphene quantum dots Macrophages Endocytosis Nuclear accumulation DNA cleavage Molecular docking |
| 研究领域 | Toxicology |
| DOI | 10.1186/s12989-018-0279-8 |
| 产权排序 | [Xu, Lina; Wang, Zhenyu] Jiangnan Univ, Inst Environm Proc & Pollut Control, Wuxi 214122, Peoples R China; [Xu, Lina; Wang, Zhenyu] Jiangnan Univ, Sch Environm & Civil Engn, Wuxi 214122, Peoples R China; [Xu, Lina; Dai, Yanhui; Zhao, Jian] Ocean Univ China, Inst Coastal Environm Pollut Control, Qingdao 266100, Peoples R China; [Xu, Lina; Dai, Yanhui; Zhao, Jian] Ocean Univ China, Minist Educ, Key Lab Marine Environm & Ecol, Qingdao 266100, Peoples R China; [Wang, Zhenyu; Zhao, Jian; Li, Fei] Qingdao Natl Lab Marine Sci & Technol, Lab Marine Ecol & Environm Sci, Qingdao 266071, Peoples R China; [Li, Fei] Chinese Acad Sci, Key Lab Coastal Zone Environm Proc & Ecol Remedia, Yantai Inst Coastal Zone Res YIC, Yantai 264003, Peoples R China; [White, Jason C.] Connecticut Agr Expt Stn, Dept Analyt Chem, New Haven, CT 06504 USA; [Xing, Baoshan] Univ Massachusetts, Stockbridge Sch Agr, Amherst, MA 01003 USA |
| 作者部门 | 海岸带环境过程实验室 |
| 英文摘要 | BackgroundGiven the tremendous potential for graphene quantum dots (QDs) in biomedical applications, a thorough understanding of the interaction of these materials with macrophages is essential because macrophages are one of the most important barriers against exogenous particles. Although the cytotoxicity and cellular uptake of graphene QDs were reported in previous studies, the interaction between nuclei and the internalized graphene QDs is not well understood. We thus systematically studied the nuclear uptake and related nuclear response associated with aminated graphene QDs (AG-QDs) exposure.ResultsAG-QDs showed modest 24-h inhibition to rat alveolar macrophages (NR8383), with a minimum inhibitory concentration (MIC) of 200g/mL. Early apoptosis was significantly increased by AG-QDs (100 and 200g/mL) exposure and played a major role in cell death. The internalization of AG-QDs was mainly via energy-dependent endocytosis, phagocytosis and caveolae-mediated endocytosis. After a 48-h clearance period, more than half of the internalized AG-QDs remained in the cellular cytoplasm and nucleus. Moreover, AG-QDs were effectively accumulated in nucleus and were likely regulated by two nuclear pore complexes genes (Kap2 and Nup98). AG-QDs were shown to alter the morphology, area, viability and nuclear components of exposed cells. Significant cleavage and cross-linking of DNA chains after AG-QDs exposure were confirmed by atomic force microscopy investigation. Molecular docking simulations showed that H-bonding and - stacking were the dominant forces mediating the interactions between AG-QDs and DNA, and were the important mechanisms resulting in DNA chain cleavage. In addition, the generation of reactive oxygen species (ROS) (e.g., center dot OH), and the up-regulation of caspase genes also contributed to DNA cleavage.ConclusionsAG-QDs were internalized by macrophages and accumulated in nuclei, which further resulted in nuclear damage and DNA cleavage. It is demonstrated that oxidative damage, direct contact via H-bonding and - stacking, and the up-regulation of caspase genes are the primary mechanisms for the observed DNA cleavage by AG-QDs. |
| 文章类型 | Article |
| 资助机构 | NSFC [41530642, 41822705, 41820104009, 41573092] ; NSF of Shandong Province [JQ201805] ; Taishan Scholars Program of Shandong Province, China [tshw20130955] ; Aoshan Talents Program ; Qingdao National Laboratory for Marine Science and Technology [2015ASTP-0S04] ; USDA-NIFA Hatch program [MAS 00475] |
| 收录类别 | SCI |
| 语种 | 英语 |
| 关键词[WOS] | MOLECULAR DOCKING ; CELLULAR UPTAKE ; IN-VITRO ; OXIDE ; APOPTOSIS ; CELLS ; ADSORPTION ; NANOPARTICLES ; SIZE ; NANOMATERIALS |
| 研究领域[WOS] | Toxicology |
| WOS记录号 | WOS:000450180100001 |
| 引用统计 | |
| 文献类型 | 期刊论文 |
| 条目标识符 | http://ir.yic.ac.cn/handle/133337/24575 |
| 专题 | 中国科学院海岸带环境过程与生态修复重点实验室_海岸带环境过程实验室 中国科学院海岸带环境过程与生态修复重点实验室 |
| 作者单位 | 1.Jiangnan Univ, Inst Environm Proc & Pollut Control, Wuxi 214122, Peoples R China; 2.Jiangnan Univ, Sch Environm & Civil Engn, Wuxi 214122, Peoples R China; 3.Ocean Univ China, Inst Coastal Environm Pollut Control, Qingdao 266100, Peoples R China; 4.Ocean Univ China, Minist Educ, Key Lab Marine Environm & Ecol, Qingdao 266100, Peoples R China; 5.Qingdao Natl Lab Marine Sci & Technol, Lab Marine Ecol & Environm Sci, Qingdao 266071, Peoples R China; 6.Chinese Acad Sci, Key Lab Coastal Zone Environm Proc & Ecol Remedia, Yantai Inst Coastal Zone Res YIC, Yantai 264003, Peoples R China; 7.Connecticut Agr Expt Stn, Dept Analyt Chem, New Haven, CT 06504 USA; 8.Univ Massachusetts, Stockbridge Sch Agr, Amherst, MA 01003 USA |
| 推荐引用方式 GB/T 7714 | Xu, Lina,Dai, Yanhui,Wang, Zhenyu,et al. Graphene quantum dots in alveolar macrophage: uptake-exocytosis, accumulation in nuclei, nuclear responses and DNA cleavage[J]. PARTICLE AND FIBRE TOXICOLOGY,2018,15:45. |
| APA | Xu, Lina.,Dai, Yanhui.,Wang, Zhenyu.,Zhao, Jian.,Li, Fei.,...&Xing, Baoshan.(2018).Graphene quantum dots in alveolar macrophage: uptake-exocytosis, accumulation in nuclei, nuclear responses and DNA cleavage.PARTICLE AND FIBRE TOXICOLOGY,15,45. |
| MLA | Xu, Lina,et al."Graphene quantum dots in alveolar macrophage: uptake-exocytosis, accumulation in nuclei, nuclear responses and DNA cleavage".PARTICLE AND FIBRE TOXICOLOGY 15(2018):45. |
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