Inhaled gold nanoparticles cause cerebral edema and upregulate endothelial aquaporin 1 expression, involving caveolin 1 dependent repression of extracellular regulated protein kinase activity
| Autor: | Yen Ju Chan, Yu Wen Cheng, Chi Hao Tsai, Ching Hao Li, Kuan Hung Lin, Ling Ling Hwang, Ching Yi Chen, Ting Ling Yen, Po Lin Liao |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
MAPK/ERK pathway
Male Gold nanoparticle Cell Survival Surface Properties Health Toxicology and Mutagenesis Caveolin 1 lcsh:Industrial hygiene. Industrial welfare Metal Nanoparticles Brain Edema Toxicology Cerebral edema Cell Line Focal adhesion 03 medical and health sciences Mice 0302 clinical medicine Endothelial cell lcsh:RA1190-1270 medicine Animals Humans Edema Particle Size Protein kinase A Extracellular Signal-Regulated MAP Kinases Protein kinase B lcsh:Toxicology. Poisons 030304 developmental biology 0303 health sciences Inhalation Exposure Mice Inbred ICR Dose-Response Relationship Drug Aquaporin 1 Chemistry Research Endothelial Cells Water Correction General Medicine medicine.disease Cell biology Endothelial stem cell ERK 030220 oncology & carcinogenesis Gold lcsh:HD7260-7780.8 |
| Zdroj: | Particle and Fibre Toxicology Particle and Fibre Toxicology, Vol 16, Iss 1, Pp 1-14 (2019) |
| ISSN: | 1743-8977 |
| Popis: | Background Gold nanoparticles (Au-NPs) have extensive applications in electronics and biomedicine, resulting in increased exposure and prompting safety concerns for human health. After absorption, nanoparticles enter circulation and effect endothelial cells. We previously showed that exposure to Au-NPs (40–50 nm) collapsed endothelial tight junctions and increased their paracellular permeability. Inhaled nanoparticles have gained significant attention due to their biodistribution in the brain; however, little is known regarding their role in cerebral edema. The present study investigated the expression of aquaporin 1 (AQP1) in the cerebral endothelial cell line, bEnd.3, stimulated by Au-NPs. Results We found that treatment with Au-NPs induced AQP1 expression and increased endothelial permeability to water. Au-NP exposure rapidly boosted the phosphorylation levels of focal adhesion kinase (FAK) and AKT, increased the accumulation of caveolin 1 (Cav1), and reduced the activity of extracellular regulated protein kinases (ERK). The inhibition of AKT (GDC-0068) or FAK (PF-573228) not only rescued ERK activity but also prevented AQP1 induction, whereas Au-NP-mediated Cav1 accumulation remained unaltered. Neither these signaling molecules nor AQP1 expression responded to Au-NPs while Cav1 was silenced. Inhibition of ERK activity (U0126) remarkably enhanced Cav1 and AQP1 expression in bEnd.3 cells. These data demonstrate that Au-NP-mediated AQP1 induction is Cav1 dependent, but requires the repression on ERK activity. Mice receiving intranasally administered Au-NPs displayed cerebral edema, significantly augmented AQP1 protein levels; furthermore, mild focal lesions were observed in the cerebral parenchyma. Conclusions These data suggest that the subacute exposure of nanoparticles might induce cerebral edema, involving the Cav1 dependent accumulation on endothelial AQP1. |
| Databáze: | OpenAIRE |
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