MG132, a proteasome inhibitor, induces human pulmonary fibroblast cell death via increasing ROS levels and GSH depletion
| Autor: | Suhn Hee Kim, Woo Hyun Park |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Cancer Research
Programmed cell death Proteasome Endopeptidase Complex MG132 animal structures Leupeptins Glutamate-Cysteine Ligase Down-Regulation macromolecular substances Biology Transfection Antioxidants human pulmonary fibroblast chemistry.chemical_compound medicine Humans Protease Inhibitors Lung Cells Cultured Cell Proliferation chemistry.chemical_classification Membrane Potential Mitochondrial reactive oxygen species Reactive oxygen species Glutathione Peroxidase Cell Death Dose-Response Relationship Drug Cell growth Superoxide Dismutase Ubiquitination General Medicine Glutathione Articles Fibroblasts Catalase Molecular biology Up-Regulation Oxidative Stress proteasome Oncology chemistry Apoptosis Proteasome inhibitor RNA Interference Growth inhibition Proteasome Inhibitors medicine.drug |
| Zdroj: | Oncology Reports |
| ISSN: | 1791-2431 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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