title: Single-walled carbon nanotubes and graphene oxides induce autophagosome accumulation and lysosome impairment in primarily cultured murine peritoneal macrophages.
abstract: The wide application of carbon nanomaterials in various fields urges in-depth understanding of the toxic effects and underlying mechanisms of these materials on biological systems. Cell autophagy was recently recognized as an important lysosome-based pathway of cell death, and autophagosome accumulation has been found to be associated with the exposure of various nanoparticles, but the underlying mechanisms are still uncertain due to the fact that autophagosome accumulation can result from autophagy induction and/or autophagy blockade. In this study, we first evaluated the toxicity of acid-functionalized single-walled carbon nanotubes and graphene oxides, and found that both carbon nanomaterials induced adverse effects in murine peritoneal macrophages, and GOs were more potent than AF-SWCNTs. Both carbon nanomaterials induced autophagosome accumulation and the conversion of LC3-I to LC3-II. However, degradation of the autophagic substrate p62 protein was also inhibited by both nanomaterials. Further analyses on lysosomes revealed that both carbon nanomaterials accumulated in macrophage lysosomes, leading to lysosome membrane destabilization, which indicates reduced autophagic degradation. The effects of AF-SWCNTs and GOs on cell autophagy revealed by this study may shed light on the potential toxic mechanism and suggest caution on their utilization.
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 10085, China. Electronic address: binwan@rcees.ac.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Wan
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 10085, China.
authors.forename: Zi-Xia
authors.initials: ZX
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 10085, China.
authors.forename: Qi-Yan
authors.initials: QY
authors.lastname: Lv
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 10085, China.
authors.forename: Ping-Xuan
authors.initials: PX
authors.lastname: Dong
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 10085, China.
authors.forename: Li-Xia
authors.initials: LX
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 10085, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 10085, China. Electronic address: LHGuo@rcees.ac.cn.
authors.forename: Liang-Hong
authors.initials: LH
authors.lastname: Guo
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D016923:Cell Death / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D005260:Female; D006108:Graphite / Q000737:chemistry / Q000633:toxicity*; D008247:Lysosomes / Q000187:drug effects* / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008815:Mice, Inbred Strains; D037742:Nanotubes, Carbon / Q000737:chemistry / Q000633:toxicity*; D010087:Oxides / Q000737:chemistry / Q000633:toxicity*; D051758:Transcription Factor TFIIH; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: C490981:Gtf2h1 protein, mouse; D037742:Nanotubes, Carbon; D010087:Oxides; D014157:Transcription Factors; D051758:Transcription Factor TFIIH; D006108:Graphite
keywords: Autophagosome accumulation; Autophagy; Carbon nanomaterials; Lysosome impairment; Macrophage