Impact of Endocytosis and Lysosomal Acidification on the Toxicity of Copper Oxide Nano- and Microsized Particles: Uptake and Gene Expression Related to Oxidative Stress and the DNA Damage Response
| Autor: | Andrea Hartwig, Bettina Maria Strauch, Wera Hubele |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Copper oxide
DNA damage General Chemical Engineering chemistry.chemical_element 02 engineering and technology lysosomal acidification Endocytosis medicine.disease_cause Article lcsh:Chemistry 03 medical and health sciences chemistry.chemical_compound cellular copper uptake medicine gene expression profiling endocytosis General Materials Science 030304 developmental biology 0303 health sciences copper oxide nanoparticles high-throughput RT-qPCR Bafilomycin Glutathione 021001 nanoscience & nanotechnology genomic stability Copper chemistry lcsh:QD1-999 Biophysics Trojan horse-type mechanism 0210 nano-technology Oxidative stress Intracellular |
| Zdroj: | Nanomaterials, Vol 10, Iss 679, p 679 (2020) Nanomaterials Volume 10 Issue 4 |
| ISSN: | 2079-4991 |
| Popis: | The toxicity of the copper oxide nanoparticles (CuO NP) has been attributed to the so-called &ldquo Trojan horse&rdquo type mechanism, relying on the particle uptake and extensive intracellular release of copper ions, due to acidic pH in the lysosomes. Nevertheless, a clear distinction between extra- and intracellular-mediated effects is still missing. Therefore, the impact of the endocytosis inhibitor hydroxy-dynasore (OH-dyn), as well as bafilomycin A1 (bafA1), inhibiting the vacuolar type H+-ATPase (V-ATPase), on the cellular toxicity of nano- and microsized CuO particles, was investigated in BEAS 2 B cells. Selected endpoints were cytotoxicity, copper uptake, glutathione (GSH) levels, and the transcriptional DNA damage and (oxidative) stress response using the high-throughput reverse transcription quantitative polymerase chain reaction (RT-qPCR). OH-dyn markedly reduced intracellular copper accumulation in the cases of CuO NP and CuO MP the modulation of gene expression, induced by both particle types affecting especially HMOX1, HSPA1A, MT1X, SCL30A1, IL8 and GADD45A, were completely abolished. BafA1 lowered the intracellular copper concentration in case of CuO NP and strongly reduced transcriptional changes, while any CuO MP-mediated effects were not affected by bafA1. In conclusion, the toxicity of CuO NP depended almost exclusively upon dynamin-dependent endocytosis and the intracellular release of redox-active copper ions due to lysosomal acidification, while particle interactions with cellular membranes appeared to be not relevant. |
| Databáze: | OpenAIRE |
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