Please confirm you are human (Sign Up for free to never see this)
← Back to Search
Formation Of Nucleoplasmic Protein Aggregates Impairs Nuclear Function In Response To SiO2 Nanoparticles.
Min Chen, A. von Mikecz
Published 2005 · Biology, Medicine
Save to my Library
Download PDFAnalyze on Scholarcy
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.
This paper references
Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease
M. Tanaka (2004)
Interference by Huntingtin and Atrophin-1 with CBP-Mediated Transcription Leading to Cellular Toxicity
F. Nucifora (2001)
Conjugation to gold nanoparticles enhances polyethylenimine's transfer of plasmid DNA into mammalian cells
Mini P. Thomas (2003)
Proteasome-dependent processing of nuclear proteins is correlated with their subnuclear localization
T. Rockel (2002)
Nanoparticulate systems for brain delivery of drugs.
J. Kreuter (2001)
Severe deficiencies in dopamine signaling in presymptomatic Huntington's disease mice.
J. Bibb (2000)
Amyloid fibers are water-filled nanotubes
M. Perutz (2002)
Morphological properties of atmospheric aerosol aggregates
C. Xiong (2001)
Eukaryotic proteasomes cannot digest polyglutamine sequences and release them during degradation of polyglutamine-containing proteins.
P. Venkatraman (2004)
Sp1 and TAFII130 Transcriptional Activity Disrupted in Early Huntington's Disease
A. Dunah (2002)
Aggresomes: A Cellular Response to Misfolded Proteins
J. A. Johnston (1998)
DNA topoisomerases: structure, function, and mechanism.
J. Champoux (2001)
Megabase Chromatin Domains Involved in DNA Double-Strand Breaks in Vivo
E. Rogakou (1999)
Protein degradation and protection against misfolded or damaged proteins
A. Goldberg (2003)
Biophysical and morphological correlates of kinetic change and death in a starved human melanoma cell line.
J. Sheridan (1981)
Toxic Proteins in Neurodegenerative Disease
J. P. Taylor (2002)
Nuclear speckles: a model for nuclear organelles
A. Lamond (2003)
The potential environmental impact of engineered nanomaterials
V. Colvin (2003)
The Huntington's disease protein interacts with p53 and CREB-binding protein and represses transcription.
J. Steffan (2000)
Fabrication of novel biomaterials through molecular self-assembly
S. Zhang (2003)
Long-circulating and target-specific nanoparticles: theory to practice.
S. Moghimi (2001)
The 22 S cylinder particles of Xenopus laevis. II. Immunological characterization and localization of their proteins in tissues and cultured cells.
B. Hügle (1983)
Nuclear pore complex is able to transport macromolecules with diameters of about 39 nm.
N. Pante (2002)
Little Big Science.
G. Stix (1999)
Nuclear and Neuropil Aggregates in Huntington’s Disease: Relationship to Neuropathology
C. Gutekunst (1999)
The ubiquitin–proteasome pathway: on protein death and cell life
A. Ciechanover (1998)
Pivotal role of oligomerization in expanded polyglutamine neurodegenerative disorders
I. Sánchez (2003)
Intracellular distribution of proteasomes.
A. Rivett (1998)
Polyglutamine fibrillogenesis: The pathway unfolds
C. Ross (2002)
Polyglutamine Pathogenesis Emergence of Unifying Mechanisms for Huntington's Disease and Related Disorders
C. Ross (2002)
Micellar Nanocontainers Distribute to Defined Cytoplasmic Organelles
R. Savić (2003)
Expansion explosion: new clues to the pathogenesis of repeat expansion neurodegenerative diseases.
R. Margolis (2001)
Intracellular Localization of Proteasomal Degradation of a Viral Antigen
L. Antón (1999)
Physico-Chemical Properties of Silica in Relation to its Toxicity
T. Nash (1966)
ER Quality Control: The Cytoplasmic Connection
R. Kopito (1997)
Structure and function of the nucleolus.
U. Scheer (1999)
Screening for proteins with polyglutamine expansions in autosomal dominant cerebellar ataxias.
G. Stevanin (1996)
Role of Promyelocytic Leukemia (Pml) Sumolation in Nuclear Body Formation, 11s Proteasome Recruitment, and as2O3-Induced Pml or Pml/Retinoic Acid Receptor α Degradation
V. Lallemand-Breitenbach (2001)
Ultrafine particles in the urban air: to the respiratory tract--and beyond?
G. Oberdörster (2002)
Proteasome inhibitors: valuable new tools for cell biologists.
D. H. Lee (1998)
Generation of major histocompatibility complex class I antigens: functional interplay between proteasomes and TPPII
P. Kloetzel (2004)
The transcriptional role of PML and the nuclear body
S. Zhong (2000)
Translocation of Inhaled Ultrafine Particles to the Brain
G. Oberdörster (2004)
Polyglutamine protein aggregates are dynamic
S. Kim (2002)
Tracking the intracellular path of poly(ethylenimine)/DNA complexes for gene delivery.
W. Godbey (1999)
Cell cycle-dependent association of PML bodies with sites of active transcription in nuclei of mammalian cells.
Almut Kiesslich (2002)
Factor required for mammalian spliceosome assembly is localized to discrete regions in the nucleus
X. Fu (1990)
Polar zippers: Their role in human disease
M. Perutz (1995)
Properties of abnormal proteins degraded rapidly in reticulocytes. Intracellular aggregation of the globin molecules prior to hydrolysis.
Y. Klemes (1981)
PARTICLE TOXICOLOGY: FROM COAL MINING TO NANOTECHNOLOGY
P. Borm (2002)
MDC1 is required for the intra-S-phase DNA damage checkpoint
M. Goldberg (2003)
The Deacetylase HDAC6 Regulates Aggresome Formation and Cell Viability in Response to Misfolded Protein Stress
Y. Kawaguchi (2003)
Aggresomes, inclusion bodies and protein aggregation.
R. Kopito (2000)
Platinum-induced autoantibodies target nucleoplasmic antigens related to active transcription.
M. Chen (2002)
Fate of abnormal proteins in E. coli accumulation in intracellular granules before catabolism.
W. Prouty (1972)
Changes in intracellular localization of proteasomes in immortalized ovarian granulosa cells during mitosis associated with a role in cell cycle control.
A. Amsterdam (1993)
Functional architecture in the cell nucleus.
M. Dundr (2001)
Dynamic organization of DNA replication in mammalian cell nuclei: spatially and temporally defined replication of chromosome-specific alpha-satellite DNA sequences
R. O'Keefe (1992)
MDC1 is a mediator of the mammalian DNA damage checkpoint
G. Stewart (2003)
Creb-Binding Protein (Cbp/P300) and RNA Polymerase II Colocalize in Transcriptionally Active Domains in the Nucleus
A. von Mikecz (2000)
Nuclear Inclusions in Glutamine Repeat Disorders Are They Pernicious, Coincidental, or Beneficial?
S. Sisodia (1998)
Nanoshell-mediated near-infrared thermal therapy of tumors under magnetic resonance guidance
L. R. Hirsch (2003)
Visions of the cell nucleus
P. Hemmerich (2005)
Distinct 19 S and 20 S subcomplexes of the 26 S proteasome and their distribution in the nucleus and the cytoplasm.
J. Peters (1994)
Specificity in intracellular protein aggregation and inclusion body formation
R. S. Rajan (2001)
Cajal bodies: the first 100 years.
J. Gall (2000)
Subcellular recruitment of fibrillarin to nucleoplasmic proteasomes: implications for processing of a nucleolar autoantigen.
M. Chen (2002)
DNA nanoparticles and development of DNA delivery vehicles for gene therapy.
V. Vijayanathan (2002)
Moving smaller in drug discovery and delivery
D. LaVan (2002)
Aggregation of proteins with expanded glutamine and alanine repeats of the glutamine-rich and asparagine-rich domains of Sup35 and of the amyloid β-peptide of amyloid plaques
M. Perutz (2002)
This paper is referenced by
Nanotechnologies in Cancer
G. De Rosa (2013)
Effects of carbon black to inflammation and oxidative DNA damages in mouse macrophages
Kyung-Taek Rim (2011)
In vitro toxicity of silica nanoparticles in human lung cancer cells.
W. Lin (2006)
Nanoparticles and Human Health: A Review of Epidemiological Studies
V. Sutariya (2014)
A new method based on electron diffraction for detecting nanoparticles in injectable medicines.
M. Gemmi (2019)
Nanotechnology: a future tool to improve quality and safety in meat industry
P. K. Singh (2015)
The PPI network and cluster ONE analysis to explain the mechanism of bladder cancer.
F. Wan (2013)
The role of surface charge in cellular uptake and cytotoxicity of medical nanoparticles
E. Fröhlich (2012)
Genotoxicity of nano-silica in mammalian cell lines
Han-Saem Choi (2011)
Comparative study of cytotoxicity, oxidative stress and genotoxicity induced by four typical nanomaterials: the role of particle size, shape and composition
H. Yang (2009)
Fate and Health Impact of Inorganic Manufactured Nanoparticles
A. Baeza-Squiban (2013)
Nanoparticles for Photodynamic Therapy of Cancer
M. Zeisser-Labouèbe (2007)
Xenobiotic-induced autoimmunity and protein aggregation diseases share a common subnuclear pathology.
A. Mikecz (2005)
Uptake and intracellular localization of submicron and nano-sized SiO2 particles in HeLa cells
Marco Al-Rawi (2010)
Biological effects induced by BSA-stabilized silica nanoparticles in mammalian cell lines.
Rasmus Foldbjerg (2013)
The implication of iron oxide nanoparticles on the removal of trichloroethylene by adsorption
H. Salih (2012)
Mechanism Of Nanoparticle And Nanotube-induced Cell Death
S. Sohaebuddin (2009)
Cellular uptake, evolution, and excretion of silica nanoparticles in human cells.
Zhiqin Chu (2011)
The β-SiC Nanowires (~100 nm) Induce Apoptosis via Oxidative Stress in Mouse Osteoblastic Cell Line MC3T3-E1
Weili Xie (2014)
Development of Taiwan’s strategies for regulating nanotechnology-based pharmaceuticals harmonized with international considerations
Jiun-Wen Guo (2014)
Multinucleation and cell dysfunction induced by amorphous silica nanoparticles in an L-02 human hepatic cell line
W. Wang (2013)
Particle-size-dependent toxicity and immunogenic activity of mesoporous silica-based adjuvants for tumor immunotherapy.
Xiupeng Wang (2013)
Iron oxide nanoparticles and induced autophagy in human monocytes
Qihong Wu (2017)
Uniwersytet Przyrodniczy we Wrocławiu Wydział Biologii i Hodowli Zwierząt
Katarzyna Czyż (2011)
Tissue distribution and excretion kinetics of orally administered silica nanoparticles in rats
J. Lee (2014)
Effects of Airborne Nanoparticles on the Nervous System: Amyloid Protein Aggregation, Neurodegeneration and Neurodegenerative Diseases
A. von Mikecz (2020)
Nanomaterials in Food and Food Contact Materials–Potential Implications for Consumer Safety and Regulatory Controls
Q. Chaudhry (2011)
Large uptake of titania and iron oxide nanoparticles in the nucleus of lung epithelial cells as measured by Raman imaging and multivariate classification.
Linnéa Ahlinder (2013)
Focusing the research efforts.
Françoise Schrurs (2012)
Nanotoxicology - an in vitro approach
M. V. D. Zee (2012)
Insights into the toxicity of iron oxides nanoparticles in land snails.
E. Sidiropoulou (2018)
Health hazards associated with nanomaterials
Gurulingappa Pattan (2014)See more