title: Titanium dioxide aggregating nanoparticles induce autophagy and under-expression of microRNA 21 and 30a in A549 cell line: A comparative study with cobalt(II, III) oxide nanoparticles.
abstract: The toxicity of TiO2nanoparticles (NPs) is controversial, while it is widely accepted for Co3O4NPs. We present a comparative study concerning the uptake of these NPs and their effect on cytoplasmic organelles and autophagy in a human lung carcinoma cell line (A549), including assays on the expression of autophagy-related microRNAs. The NP accumulation caused a fast dose- and time-dependent change of flow cytometry physical parameters particularly after TiO2NP exposure. The intracellular levels of metals confirmed it, but the Co concentration was ten times higher than that of Ti. Both NPs caused neither necrosis nor apoptosis, but cytotoxicity was mainly evident for Co3O4NPs in the first 72h. TiO2NPs caused autophagy, contrarily to Co3O4NPs. Furthermore, a significant and persistent downregulation of miRNA-21 and miRNA-30a was observed only in TiO2NPs-treated cultures. The expression of miRNA-155 was similar for both NPs. Oxidative stress was evident only for Co3O4NPs, while both NPs perturbed endoplasmic reticulum and p-53 expression. In conclusion, the oxidative stress caused by Co3O4NPs can influence energy homeostasis and hamper the ability to detoxify and to repair the resulting damage, thus preventing the induction of autophagy, while TiO2NPs elicit autophagy also under sub-toxic conditions.
authors.affiliation: Department of Medicine and Surgery, University of Parma, Parma, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Alinovi
authors.affiliation: Department of Medicine and Surgery, University of Parma, Parma, Italy. Electronic address: matteo.goldoni@unipr.it.
authors.forename: Matteo
authors.initials: M
authors.lastname: Goldoni
authors.affiliation: Department of Medicine and Surgery, University of Parma, Parma, Italy.
authors.forename: Silvana
authors.initials: S
authors.lastname: Pinelli
authors.affiliation: Department of Medical Veterinary Sciences, Unit of Normal Veterinary Anatomy, University of Parma, Parma, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ravanetti
authors.affiliation: Italian Workers' Compensation Authority (INAIL) Research Center, Parma, Italy.
authors.forename: Maricla
authors.initials: M
authors.lastname: Galetti
authors.affiliation: Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Pelosi
authors.affiliation: Section of Public Health and Human Sciences, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: De Palma
authors.affiliation: Section of Public Health and Human Sciences, Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Apostoli
authors.affiliation: Department of Medical Veterinary Sciences, Unit of Normal Veterinary Anatomy, University of Parma, Parma, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Cacchioli
authors.affiliation: Department of Medicine and Surgery, University of Parma, Parma, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Mutti
authors.affiliation: Department of Medicine and Surgery, University of Parma, Parma, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Mozzoni
mesh_terms: D000072283:A549 Cells; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D001692:Biological Transport; D001798:Blood Proteins / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D003035:Cobalt / Q000633:toxicity*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins / Q000378:metabolism; D006801:Humans; D053768:Metal Nanoparticles / Q000633:toxicity*; D035683:MicroRNAs / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010087:Oxides / Q000633:toxicity*; D014025:Titanium / Q000633:toxicity*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D001798:Blood Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; C524942:MIRN155 microRNA, human; C524940:MIRN21 microRNA, human; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D010087:Oxides; D016159:Tumor Suppressor Protein p53; C009495:titanium dioxide; D003035:Cobalt; D014025:Titanium; C060728:cobalt oxide
keywords: Autophagy; Co(3)O(4); Nanoparticles; Oxidative stress; TiO(2); microRNA