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Article

MG132, a proteasome inhibitor, induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion

  • Authors:
    • Woo Hyun Park
    • Suhn Hee Kim
  • View Affiliations / Copyright

    Affiliations: Department of Physiology, Medical School, Chonbuk National University, Jeonju 561-180, Republic of Korea
  • Pages: 1284-1291
    |
    Published online on: January 19, 2012
       https://doi.org/10.3892/or.2012.1642
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Abstract

MG132 as a proteasome inhibitor can induce apoptotic cell death in lung cancer cells. However, little is known about the toxicological cellular effects of MG132 on normal primary lung cells. Here, we investigated the effects of N-acetyl cysteine (NAC) and vitamin C (well known antioxidants) or L-buthionine sulfoximine (BSO; an inhibitor of GSH synthesis) on MG132-treated human pulmonary fibroblast (HPF) cells in relation to cell death, reactive oxygen species (ROS) and glutathione (GSH). MG132 induced growth inhibition and death in HPF cells, accompanied by the loss of mitochondrial membrane potential (MMP; ∆ψm). MG132 increased ROS levels and GSH-depleted cell numbers in HPF cells. Both antioxidants, NAC and vitamin C, prevented growth inhibition, death and MMP (∆ψm) loss in MG132-treated HPF cells and also attenuated ROS levels in these cells. BSO showed a strong increase in ROS levels in MG132-treated HPF cells and slightly enhanced the growth inhibition, cell death, MMP (∆ψm) loss and GSH depletion. In addition, NAC decreased anonymous ubiquitinated protein levels in MG132-treated HPF cells. Furthermore, superoxide dismutase (SOD) 2, catalase (CTX) and GSH peroxidase (GPX) siRNAs enhanced HPF cell death by MG132, which was not correlated with ROS and GSH level changes. In conclusion, MG132 induced the growth inhibition and death of HPF cells, which were accompanied by increasing ROS levels and GSH depletion. Both NAC and vitamin C attenuated HPF cell death by MG132, whereas BSO slightly enhanced the death.
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Copy and paste a formatted citation
Spandidos Publications style
Park WH and Kim SH: MG132, a proteasome inhibitor, induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion. Oncol Rep 27: 1284-1291, 2012.
APA
Park, W.H., & Kim, S.H. (2012). MG132, a proteasome inhibitor, induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion. Oncology Reports, 27, 1284-1291. https://doi.org/10.3892/or.2012.1642
MLA
Park, W. H., Kim, S. H."MG132, a proteasome inhibitor, induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion". Oncology Reports 27.4 (2012): 1284-1291.
Chicago
Park, W. H., Kim, S. H."MG132, a proteasome inhibitor, induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion". Oncology Reports 27, no. 4 (2012): 1284-1291. https://doi.org/10.3892/or.2012.1642
Copy and paste a formatted citation
x
Spandidos Publications style
Park WH and Kim SH: MG132, a proteasome inhibitor, induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion. Oncol Rep 27: 1284-1291, 2012.
APA
Park, W.H., & Kim, S.H. (2012). MG132, a proteasome inhibitor, induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion. Oncology Reports, 27, 1284-1291. https://doi.org/10.3892/or.2012.1642
MLA
Park, W. H., Kim, S. H."MG132, a proteasome inhibitor, induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion". Oncology Reports 27.4 (2012): 1284-1291.
Chicago
Park, W. H., Kim, S. H."MG132, a proteasome inhibitor, induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion". Oncology Reports 27, no. 4 (2012): 1284-1291. https://doi.org/10.3892/or.2012.1642
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