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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

Strauch, B. M.; Hubele, W.; Hartwig, A.

Abstract:
The toxicity of the copper oxide nanoparticles (CuO NP) has been attributed to the so-called “Trojan horse”-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. ... mehr

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Verlagsausgabe §
DOI: 10.5445/IR/1000118969
Veröffentlicht am 18.05.2020
Cover der Publikation
Zugehörige Institution(en) am KIT Institut für Angewandte Biowissenschaften (IAB)
Publikationstyp Zeitschriftenaufsatz
Publikationsjahr 2020
Sprache Englisch
Identifikator ISSN: 2079-4991
KITopen-ID: 1000118969
Erschienen in Nanomaterials
Band 10
Heft 4
Seiten Article: 679
Schlagwörter copper oxide nanoparticles; genomic stability; gene expression profiling; high-throughput RT-qPCR; endocytosis; cellular copper uptake; lysosomal acidification; Trojan horse-type mechanism
Nachgewiesen in Scopus
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