title: Toxicity of carboxylated carbon nanotubes in endothelial cells is attenuated by stimulation of the autophagic flux with the release of nanomaterial in autophagic vesicles.
abstract: Carbon nanotubes (CNTs) exhibit a number of unique properties that make them attractive for various nanomedicine applications including their intravascular use. Therefore, the vascular toxicity of CNTs is a critical safety concern and methods of CNTs toxicity modulation are of great interest. Here, we report that carboxylated multiwalled carbon nanotubes (MWCNTs) induce a decrease in viability of cultured human umbilical vein endothelial cells (HUVECs) associated with the profound accumulation of autophagosomes. This autophagosome accumulation was mTOR kinase independent and was caused by blockade of the autophagic flux rather than by activation of autophagy. Stimulation of the autophagic flux with 1nmol/L bafilomycin A1 attenuated the cytotoxicity of carboxylated MWCNTs in HUVECs and was associated with the extracellular release of the nanomaterial in autophagic microvesicles. Thus, pharmacological stimulation of the autophagic flux may represent a new method of cytoprotection against toxic effects of nanomaterials.
  
  
  BACKGROUND
  This study investigates the mechanisms of toxicity of multiwalled carbon nanutubes on human endothelial cells, concluding that pharmacological stimulation of autophagic flux may represent a new method of cytoprotection against the toxic effects of these nanomaterials.
authors.affiliation: Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD, USA.
authors.forename: Martina
authors.initials: M
authors.lastname: Orecna
authors.affiliation: Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD, USA.
authors.forename: Silvia H
authors.initials: SH
authors.lastname: De Paoli
authors.affiliation: Institute of Immunology and Microbiology, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic; Institute of Macromolecular Chemistry, Academy of Sciences of the Czech Republic, Prague Czech Republic.
authors.forename: Olga
authors.initials: O
authors.lastname: Janouskova
authors.affiliation: Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD, USA.
authors.forename: Tseday Z
authors.initials: TZ
authors.lastname: Tegegn
authors.affiliation: Institute of Immunology and Microbiology, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Marcela
authors.initials: M
authors.lastname: Filipova
authors.affiliation: National Institute of Standards and Technology, Gaithersburg, MD, USA.
authors.forename: John E
authors.initials: JE
authors.lastname: Bonevich
authors.affiliation: Institute of Immunology and Microbiology, 1st Faculty of Medicine, Charles University in Prague, Prague, Czech Republic.
authors.forename: Karel
authors.initials: K
authors.lastname: Holada
authors.affiliation: Center for Biologics Evaluation and Research, Food and Drug Administration, Rockville, MD, USA. Electronic address: jan.simak@fda.hhs.gov.
authors.forename: Jan
authors.initials: J
authors.lastname: Simak
mesh_terms: D001343:Autophagy / Q000502:physiology; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005089:Exocytosis / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D018942:Macrolides / Q000494:pharmacology; D049329:Nanostructures / Q000633:toxicity*; D037742:Nanotubes, Carbon
chemical_list: D018942:Macrolides; D037742:Nanotubes, Carbon; C040929:bafilomycin A1
keywords: Autophagy; Bafilomycin A1; Carbon nanotubes; Exocytosis; Microvesicles