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Research ArticleToxicology

Cerium Oxide Nanoparticles Inhibits Oxidative Stress and Nuclear Factor-κB Activation in H9c2 Cardiomyocytes Exposed to Cigarette Smoke Extract

Jianli Niu, Kangkai Wang and Pappachan E. Kolattukudy
Journal of Pharmacology and Experimental Therapeutics July 2011, 338 (1) 53-61; DOI: https://doi.org/10.1124/jpet.111.179978
Jianli Niu
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Kangkai Wang
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Pappachan E. Kolattukudy
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Abstract

Cigarette smoke contains and generates a large amount of reactive oxygen species (ROS) that affect normal cellular function and have pathogenic consequences in the cardiovascular system. Increased oxidative stress and inflammation are considered to be an important mechanism of cardiovascular injury induced by cigarette smoke. Antioxidants may serve as effective therapeutic agents against smoke-related cardiovascular disease. Because of the presence of oxygen vacancies on its surface and self-regenerative cycle of its dual oxidation states, Ce3+ and Ce4+, cerium oxide (CeO2) nanoparticles offer a potential to quench ROS in biological systems. In this study, we determined the ability of CeO2 nanoparticles to protect against cigarette smoke extract (CSE)-induced oxidative stress and inflammation in cultured rat H9c2 cardiomyocytes. CeO2 nanoparticles pretreatment of H9c2 cells resulted in significant inhibition of CSE-induced ROS production and cell death. Pretreatment of H9c2 cells with CeO2 nanoparticles suppressed CSE-induced phosphorylation of IκBα, nuclear translocation of p65 subunit of nuclear factor-κB (NF-κB), and NF-κB reporter activity in H9c2 cells. CeO2 nanoparticles pretreatment also resulted in a significant down-regulation of NF-κB-regulated inflammatory genes tumor necrosis factor-α, interleukin (IL)-1β, IL-6, and inducible nitric-oxide synthase and further inhibited CSE-induced depletion of antioxidant enzymes, such as copper zinc superoxide dismutase, manganese superoxide dismutase, and intracellular glutathione content. These results indicate that CeO2 nanoparticles can inhibit CSE-induced cell damage via inhibition of ROS generation, NF-κB activation, inflammatory gene expression, and antioxidant depletion and may have a great potential for treatment of smoking-related diseases.

Footnotes

  • This work was supported by the National Institutes of Health National Heart, Lung, and Blood Institute [Grant HL69458].

  • Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.

    doi:10.1124/jpet.111.179978.

  • ABBREVIATIONS:

    ROS
    reactive oxygen species
    CeO2
    cerium oxide
    NF-κB
    nuclear factor-κB
    IκBα
    inhibitor of κBα
    CSE
    cigarette smoke extract
    MCP-1
    monocyte chemotactic protein-1
    TNF-α
    tumor necrosis factor-α
    IL-1β
    interleukin-1β
    IL-6
    interleukin-6
    iNOS
    inducible nitric-oxide synthase
    SOD
    superoxide dismutase
    CuZnSOD
    copper zinc SOD
    MnSOD
    manganese SOD
    FBS
    fetal bovine serum
    DMEM
    Dulbecco's modified Eagle's medium
    DPBS
    Dulbecco's phosphate-buffered saline
    DHR123
    dihydrorhodamine 123
    RT-PCR
    reverse transcriptase-polymerase chain reaction
    TUNEL
    TdT-mediated dUTP nick-end-labeling
    TMR
    tetramethylrhodamine
    Z-DEVD-R110
    bis-(N-CBZ-l-aspartyl-l-glutamyl-l-valyl-aspartic acid amide

  • Received January 26, 2011.
  • Accepted March 30, 2011.
  • Copyright © 2011 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 338 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 338, Issue 1
1 Jul 2011
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Research ArticleToxicology

Cerium Oxide Nanoparticles Inhibits Oxidative Stress and Nuclear Factor-κB Activation in H9c2 Cardiomyocytes Exposed to Cigarette Smoke Extract

Jianli Niu, Kangkai Wang and Pappachan E. Kolattukudy
Journal of Pharmacology and Experimental Therapeutics July 1, 2011, 338 (1) 53-61; DOI: https://doi.org/10.1124/jpet.111.179978

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Research ArticleToxicology

Cerium Oxide Nanoparticles Inhibits Oxidative Stress and Nuclear Factor-κB Activation in H9c2 Cardiomyocytes Exposed to Cigarette Smoke Extract

Jianli Niu, Kangkai Wang and Pappachan E. Kolattukudy
Journal of Pharmacology and Experimental Therapeutics July 1, 2011, 338 (1) 53-61; DOI: https://doi.org/10.1124/jpet.111.179978
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