Involvement of mtROS and Warburg effect in diabetic complications progression mechanism by hypoglycemia
| Project/Area Number |
15K09393
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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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 |
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| Co-Investigator(Kenkyū-buntansha) |
荒木 栄一 熊本大学, 大学院生命科学研究部(医), 教授 (10253733)
松村 剛 熊本大学, 大学院生命科学研究部(医), 准教授 (20398192)
西川 武志 熊本大学, 大学院生命科学研究部(医), 特任准教授 (70336212)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | ミトコンドリア由来活性酸素種 / 低血糖 / 糖尿病 / 動脈硬化 / 糖尿病細小血管合併症 / 糖尿病網膜症 / ミトコンドリアROS / β酸化 |
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| Outline of Final Research Achievements |
Results: We found that low glucose (LG) increased mtROS generation in endotherial cells (ECs); this effect was suppressed by overexpression of manganese superoxide dismutase (MnSOD). Comprehensive metabolic analysis using capillary electrophoresis-mass spectrometry and oxygen consumption rate assessment revealed that the pathway from fatty acid to acetyl-CoA via fatty acid oxidation (FAO) was upregulated in ECs under LG. In addition, etomoxir, a specific inhibitor of the free fatty acid transporter, decreased LG-induced mtROS production. These results suggested that LG increased mtROS generation through activation of FAO. We further revealed that LG inhibited eNOS phosphorylation and increased the expression of VCAM-1 and ICAM-1. These effects were prevented either by overexpression of MnSOD or by etomoxir.
Conclusions: These findings suggested that activation of FAO followed by mtROS production could be a novel therapeutic target for endothelial dysfunction during hypoglycemia.
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Report
(4 results)
Research Products
(9 results)
