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Next‐Generation Sequencing Reveals Differential Responses to Acute versus Long‐Term Exposures to Graphene Oxide in Human Lung Cells
Author(s) -
Mukherjee Sourav P.,
Gupta Govind,
Klöditz Katharina,
Wang Jun,
Rodrigues Artur Filipe,
Kostarelos Kostas,
Fadeel Bengt
Publication year - 2020
Publication title -
small
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.785
H-Index - 236
eISSN - 1613-6829
pISSN - 1613-6810
DOI - 10.1002/smll.201907686
Subject(s) - apoptosis , downregulation and upregulation , gene , graphene , lung , biology , microbiology and biotechnology , medicine , genetics , materials science , nanotechnology
Numerous studies have addressed the biological impact of graphene‐based materials including graphene oxide (GO), yet few have focused on long‐term effects. Here, RNA sequencing is utilized to unearth responses of human lung cells to GO. To this end, the BEAS‐2B cell line derived from normal human bronchial epithelium is subjected to repeated, low‐dose exposures of GO (1 or 5 µg mL −1 ) for 28 days or to the equivalent, cumulative amount of GO for 48 h. Then, samples are analyzed by using the NovaSeq 6000 sequencing system followed by pathway analysis and gene ontology enrichment analysis of the differentially expressed genes. Significant differences are seen between the low‐dose, long‐term exposures and the high‐dose, short‐term exposures. Hence, exposure to GO for 48 h results in mitochondrial dysfunction. In contrast, exposure to GO for 28 days is characterized by engagement of apoptosis pathways with downregulation of genes belonging to the inhibitor of apoptosis protein (IAP) family. Validation experiments confirm that long‐term exposure to GO affects the apoptosis threshold in lung cells, accompanied by a loss of IAPs. These studies reveal the sensitivity of RNA‐sequencing approaches and show that acute exposure to GO is not a good predictor of the long‐term effects of GO.