title: Magnetite nanoparticles induced adaptive mechanisms counteract cell death in human pulmonary fibroblasts.
abstract: Magnetite nanoparticles (MNP) have attracted great interest for biomedical applications due to their unique chemical and physical properties, but the MNP impact on human health is not fully known. Consequently, our study proposes to highlight the biochemical mechanisms that underline the toxic effects of MNP on a human lung fibroblast cell line (MRC-5). The cytotoxicity generated by MNP in MRC-5 cells was dose and time-dependent. MNP-treated MRC-5 cells accumulated large amount of iron and reactive oxygen species (ROS) and exhibited elevated antioxidant scavenger enzymes. Reduced glutathione (GSH) depletion and enhanced lipid peroxidation (LPO) processes were also observed. The cellular capacity to counteract the oxidative damage was sustained by high levels of heat shock protein 60 (Hsp60), a protein that confers resistance against ROS attack and inhibition of cell death. While significant augmentations in nitric oxide (NO) and prostaglandine E2 (PGE2) levels were detected after 72 h of MNP-exposure only, caspase-1 was activated earlier starting with 24h post-treatment. Taken together, our results suggest that MRC-5 cells have the capacity to develop cell protection mechanisms against MNP. Detailed knowledge of the mechanisms induced by MNP in cell culture could be essential for their prospective use in various in vivo biochemical applications.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Bucharest, 91-95 Splaiul Independentei, Bucharest 050095, Romania; Department of Histology, Faculty of Medicine, Pharmacy and Dentistry, Vasile Goldis Western University of Arad, 1 Feleacului, Arad 310396, Romania.
authors.forename: Mihaela
authors.initials: M
authors.lastname: Radu
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Bucharest, 91-95 Splaiul Independentei, Bucharest 050095, Romania.
authors.forename: Diana
authors.initials: D
authors.lastname: Dinu
authors.affiliation: Laser Department, National Institute of Laser, Plasma and Radiation Physics, 409 Atomistilor, Bucharest-Magurele 077125, Romania.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Sima
authors.affiliation: Department of Mathematics, University of Agriculture Sciences and Veterinary Medicine, 59 Marasti, Bucharest 011464, Romania.
authors.forename: Radu
authors.initials: R
authors.lastname: Burlacu
authors.affiliation: Department of Histology, Faculty of Medicine, Pharmacy and Dentistry, Vasile Goldis Western University of Arad, 1 Feleacului, Arad 310396, Romania; Department of Experimental and Applied Biology, Institute of Life Sciences, Vasile Goldis Western University of Arad, 86 Rebreanu, Arad 310414, Romania.
authors.forename: Anca
authors.initials: A
authors.lastname: Hermenean
authors.affiliation: Department of Experimental and Applied Biology, Institute of Life Sciences, Vasile Goldis Western University of Arad, 86 Rebreanu, Arad 310414, Romania.
authors.forename: Aurel
authors.initials: A
authors.lastname: Ardelean
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Bucharest, 91-95 Splaiul Independentei, Bucharest 050095, Romania. Electronic address: ancadinischiotu@yahoo.com.
authors.forename: Anca
authors.initials: A
authors.lastname: Dinischiotu
mesh_terms: D020170:Caspase 1 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D018834:Chaperonin 60 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006801:Humans; D008168:Lung / Q000166:cytology; D058185:Magnetite Nanoparticles / Q000633:toxicity*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D018834:Chaperonin 60; C060293:HSPD1 protein, human; D058185:Magnetite Nanoparticles; D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D020170:Caspase 1; D015232:Dinoprostone
keywords: Caspase-1; Hsp60; MRC-5 cells; Magnetite nanoparticles; Oxidative stress; PGE2