1. Single-walled carbon nanotubes and graphene oxides induce autophagosome accumulation and lysosome impairment in primarily cultured murine peritoneal macrophages.
- Author
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Wan B, Wang ZX, Lv QY, Dong PX, Zhao LX, Yang Y, and Guo LH
- Subjects
- Animals, Cell Death drug effects, Cell Survival, Cells, Cultured, Female, Graphite chemistry, Lysosomes metabolism, Macrophages, Peritoneal cytology, Mice, Mice, Inbred Strains, Nanotubes, Carbon chemistry, Oxides chemistry, Transcription Factor TFIIH, Transcription Factors genetics, Transcription Factors metabolism, Autophagy drug effects, Graphite toxicity, Lysosomes drug effects, Macrophages, Peritoneal drug effects, Nanotubes, Carbon toxicity, Oxides toxicity
- 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., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2013
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