2007 Fiscal Year Final Research Report Summary
Impact of mitochondria reactive oxygen species in the pathogenesis of diabetic macro- and micro vascular complications.
| Project/Area Number |
18590995
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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 |
Metabolomics
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| Research Institution | Kumamoto University |
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Principal Investigator |
NISHIKAWA Takeshi Kumamoto University, Faculty of Medical and Phamaceutical sciences, Assistant Professor (70336212)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIDA Kenro Kumamoto University, Faculty of Medical and Phamaceutical sciences, Lecturer (50336244)
MATSUMURA Takeshi Kumamoto University, University Hospital, Clinical Fellow (20398192)
MOTOSHIMA Hiroyuki Kumamoto University, University Hospital, Clinical Fellow (40398201)
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| Project Period (FY) |
2006 – 2007
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| Keywords | Diabetes Mellitus / Diabetic complications / Mitochondria / Oxidative stress / MnSOD / PPARγ / MnSOD |
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| Research Abstract |
We previously proposed that hyperglycemia-induced mitochondrial ROS overproduction is a key event in the development of diabetic complications. During 2006-2007, we have performed below project based on our hypothesis.
In this study, we established a novel transgenic mouse (eMnSOD-Tg), which specifically expressed MnSOD in endothelial cells, by employing a Tie2 promoter/enhancer, and investigated the impact of mitochondrial ROS production on diabetic retinopathy in vivo. Using immunohistochemistry, overexpression of MnSOD in endothelial cells was confirmed in eMnSOD-Tg mice. By introduction of diabetes by streptozotocin, levels of urinary 8-hydroxydeoxyguanosine, a marker of mitochondrial oxidative stress, and expression of VEGF mRNA and protein and fibronectin mRNA in retinas were increased in wild-type littermates. However, these observations were ameliorated in eMnSOD-Tg mice, although control and eMnSOD-Tg mice showed a comparable level of hyperglycemia. In the present study, we newly developed a line of transgenic mice, which specifically express MnSOD in endothelium. In addition, overexpression of mitochondrial-specific SOD in endothelium could prevent diabetic retinopathy in vivo.
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Research Products
(22 results)
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[Journal Article] Endothelial MnSOD overexpression prevents retinal VEGF expression in diabetic mice2008
Author(s)
Goto, H., Nishikawa, T.*, Sonoda, K., Kondo, T., Kukidome, D., Fujisawa, K., Yamashiro, T., Motoshima, H., Matsumura, T., Tsuruzoe, K., Araki, E.
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Journal Title
Biochem Biophys Res Commun 366
Pages: 814-820
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Oxidized low density lipoprotein activates peroxisome proliferator-activated receptor-a(PPARa) and PPARy through MAPK-dependent COX-2 expression in macrophages.2008
Author(s)
Taketa, K., Matsumura, T., Yano, M., Ishii, N., Senokuchi, T., Motoshima, H., Murata, Y., Kim-Mitsuyama, S., Kawada, T., Itabe, H., Takeya, M., Nishikawa, T., Tsuruzoe, K., Araki, E.
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Journal Title
J Biol Chem 283
Pages: 9852-9862
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Impact of mitochondrial ROS production on diabetic vascular complications.(* corresponding author)2007
Author(s)
Nishikawa, T.*, Kukidome, D., Sonoda, K., Fujisawa, K., Matsuhisa, T., Motoshima, H., Matsumura, T., Araki, E.
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Journal Title
Diabetes Res Clin Prat 77S
Pages: S41-S45
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Impact of mitochondrial ROS production in the pathogenesis of insulin resistance.(* corresponding author)2007
Author(s)
Nishikawa, T.*, Kukidome, D., Sonoda, K., Fujisawa, K., Matsuhisa, T., Motoshima, H., Matsumura, T., Araki, E.
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Journal Title
Diabetes Res Clin Pract77S
Pages: S161-S164
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Troglitazone inhibits oxidized low-density lipoprotein-induced macrophage proliferation : impact of the suppression of nuclear translocation of ERK1/22007
Author(s)
Yano, M., Matsumura, T., Senokuchi, T., Ishii, N., Motoshima, H., Taguchi, T., Matsuo, T., Sonoda, K., Kukidome, D., Sakai, M., Kawada, T., Nishikawa, N., Araki, E.
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Journal Title
Atherosclerosis 191
Pages: 22-32
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Statins activate peroxisome proliferator-activated receptor gamma through extracellular signal-regulated kinase 1/2 and p38 mitogen-activated protein kinase-dependent cyclooxygenase-2 expression in macrophages.2007
Author(s)
Yano, M., Matsumura, T., Senokuchi, T., Ishii, N., Murata, Y., Taketa, K., Motoshima, H., Taguchi, T., Sonoda, K., Kukidome, D., Takuwa, Y., Kawada, T., Brownlee, M., Nishikawa, T., Araki, E.
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Journal Title
Circ Res 100
Pages: 1442-1451
Description
「研究成果報告書概要(欧文)」より
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[Presentation] 合併症のメカニズム2006
Author(s)
西川 武志
Organizer
第44回日本糖尿病学会九州地方会
Place of Presentation
熊本
Year and Date
2006-10-13
Description
「研究成果報告書概要(和文)」より
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