2001 Fiscal Year Final Research Report Summary
Overexpression of glutathione reductase protects cells from oxidant injuries: A possible treatment for interstitial pneumonia
| Project/Area Number |
12670764
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
TAMURA Toshiya Faculty of Medicine, University of the Ryukyus, Department of Pediatrics, Research Associate, 医学部・付属病院・小児科, 助手 (70315480)
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| Co-Investigator(Kenkyū-buntansha) |
MATUURA Toshinobu Faculty of Medicine, University of the Ryukyus, Department of Pediatrics, Associate Professor, 医学部・小児科, 助教授 (00315467)
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| Project Period (FY) |
2000 – 2001
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| Keywords | antioxidant enzyme / interstitial pneumonia / glutathione reductase |
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| Research Abstract |
Interstitial pneumonia is caused by many conditions such as viral infections, chemotherapy or radiation for malignant diseases. Some cases of interstitial pneumonia complicate emphysema and pulmonary fibrosis, both of which can be fatal. Oxidant injuries and proliferation of fibroblast mediated by cytokines or growth factors are involved in the development of such complications. The final goal of this study is establishing a new treatment for interstitial pneumonia using an antioxidant enzyme.Glutathione reductase (GR) is one of the key antioxidant enzymes in the pulmonary, which catalyzes the reduction of glutathione disulfide (GSSG) to glutathione (GSH). To investigate the effects of overexpression of GR against oxidant injuries, human GR cDNA was transfected to Chinese hamster ovary (CHO) cells with or without mitochondrial targeting signal (MTS) cDNA, and stable cell lines that overexpressed GR in cytosol and/or mitochondria were isolated. One cell line G20 transfected with human GR cDNA without MTS had 5-fold higher cytosolic GR activities than CHO cells, while the other cell line GL13 transfected with human GR cDNA with MTS had 5-fold higher cytosolic GR activities and more than 10-fold higher mitochondrial GR activities. Exposure of these cell lines to t-butyl hydroperoxide or diquat which potentially causes pulmonary fibrosis demonstrated mush stronger protection in GL13 cells by the GR overexpression than in CHO cells and G20 cells, indicating that overexpression of mitochondrial GR is particularly critical for the protection from oxidant injuries.
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