title: Nanoceria protects from alterations in oxidative metabolism and calcium overloads induced by TNFα and cycloheximide in U937 cells: pharmacological potential of nanoparticles.
abstract: The present study is aimed to determine the protective effect of a novel nanoparticle with antioxidant properties, nanoceria, on reactive oxygen species (ROS) production, and calcium signaling evoked by the tumor necrosis factor-alpha (TNFα) in combination with cycloheximide (CHX) on apoptosis in the human histiocytic lymphoma cell line U937. Our results show that treatment of U937 cells with 10 ng/mL TNFα in combination with 1 μg/mL CHX led to several Ca(2+) alterations. These stimulatory effects on calcium signals were followed by intracellular ROS production and mitochondria membrane depolarization, as well as a time-dependent increase in caspase-8 and -9 activities. Our results show that the pretreatment with well known antioxidants such as trolox and N-acetyl cysteine (NAC) partially reduced the apoptotic effects due to the administration of TNFα plus cycloheximide. Furthermore, nanoceria had a stronger protective effect than trolox or NAC. Our findings also suggest that TNFα plus cycloheximide-induced apoptosis is dependent on alterations in cytosolic concentration of calcium [Ca(2+)]c and ROS generation in human histiocytic U937 cells.
authors.affiliation: Department of Physiology, Neuroimmunophysiology and Chrononutrition Research Group, Faculty of Science, University of Extremadura, 06006, Badajoz, Spain, eolis2@hotmail.com.
authors.forename: David
authors.initials: D
authors.lastname: González-Flores
authors.forename: Milena
authors.initials: M
authors.lastname: De Nicola
authors.forename: Emanuele
authors.initials: E
authors.lastname: Bruni
authors.forename: Fanny
authors.initials: F
authors.lastname: Caputo
authors.forename: Ana B
authors.initials: AB
authors.lastname: Rodríguez
authors.forename: José A
authors.initials: JA
authors.lastname: Pariente
authors.forename: Lina
authors.initials: L
authors.lastname: Ghibelli
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002118:Calcium / Q000378:metabolism*; D002563:Cerium / Q000494:pharmacology*; D002839:Chromans / Q000494:pharmacology; D003513:Cycloheximide / Q000494:pharmacology*; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D053758:Nanoparticles; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D020298:U937 Cells
chemical_list: D000935:Antifungal Agents; D002839:Chromans; D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D002563:Cerium; C030583:ceric oxide; D003513:Cycloheximide; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D002118:Calcium; D000111:Acetylcysteine