Molecular and Cellular Biochemistry

, Volume 397, Issue 1–2, pp 245–253 | Cite as

Nanoceria protects from alterations in oxidative metabolism and calcium overloads induced by TNFα and cycloheximide in U937 cells: pharmacological potential of nanoparticles

  • David González-Flores
  • Milena De Nicola
  • Emanuele Bruni
  • Fanny Caputo
  • Ana B. Rodríguez
  • José A. Pariente
  • Lina Ghibelli
Article
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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 Ca2+ 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 [Ca2+]c and ROS generation in human histiocytic U937 cells.

Keywords

TNF-α Apoptosis Calcium Antioxidants Nanoparticles U937 cells 
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Notes

Acknowledgments

This work was supported by MICINN-FEDER (BFU 2010-15049) and 2008 PRIN Project “miRNA in diagnosis and experimental therapy via nano-vectors of pleural malignant mesothelioma” of the Italian Ministry of Education, University and Research (MIUR). Thanks to Prof. Enrico Traversa, Dipartamento di Scienze e Tecnologie Chimiche, Università si Roma Tor-Vergata, for providing nanoceria and scientific support.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • David González-Flores
    • 1
  • Milena De Nicola
    • 2
  • Emanuele Bruni
    • 2
  • Fanny Caputo
    • 3
  • Ana B. Rodríguez
    • 1
  • José A. Pariente
    • 1
  • Lina Ghibelli
    • 2
  1. 1.Department of Physiology, Neuroimmunophysiology and Chrononutrition Research Group, Faculty of ScienceUniversity of ExtremaduraBadajozSpain
  2. 2.Dipartimento di BiologiaUniversità di Tor Vergata, Via della Ricerca ScientificaRomeItaly
  3. 3.Dipartimento di Scienze e Tecnologie ChimicheUniversità di Tor Vergata, Via della Ricerca ScientificaRomeItaly

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