Formation of nucleoplasmic protein aggregates impairs nuclear function in response to SiO2 nanoparticles.
Despite of their exponentially growing use, little is known about cell biological effects of nanoparticles. Here, we report uptake of silica (SiO(2)) nanoparticles to the cell nucleus where they induce aberrant clusters of topoisomerase I (topo I) in the nucleoplasm that additionally contain signature proteins of nuclear domains, and protein aggregation such as ubiquitin, proteasomes, cellular glutamine repeat (polyQ) proteins, and huntingtin. Formation of intranuclear protein aggregates (1) inhibits replication, transcription, and cell proliferation; (2) does not significantly alter proteasomal activity or cell viability; and (3) is reversible by Congo red and trehalose. Since SiO(2) nanoparticles trigger a subnuclear pathology resembling the one occurring in expanded polyglutamine neurodegenerative disorders, we suggest that integrity of the functional architecture of the cell nucleus should be used as a read out for cytotoxicity and considered in the development of safe nanotechnology.
Chen
Min
M
Institut für umweltmedizinische Forschung (IUF) at Heinrich-Heine-University Düsseldorf, Auf'm Hennekamp 50, D-40225 Düsseldorf, Germany.
von Mikecz
Anna
A
D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects / Q000502:physiology; D004847:Epithelial Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D007700:Kinetics; D009687:Nuclear Proteins / Q000187:drug effects / Q000502:physiology*; D012822:Silicon Dioxide / Q000494:pharmacology*; D014158:Transcription, Genetic
D009687:Nuclear Proteins; D012822:Silicon Dioxide