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Glyoxalase I overexpression ameliorates renal ischemia-reperfusion injury in rats
https://doi.org/10.15083/00002318
https://doi.org/10.15083/0000231862452833-cdb7-4d7b-8e8b-3b1056b714b8
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
41_57421.pdf (3.0 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2012-03-01 | |||||
| タイトル | ||||||
| タイトル | Glyoxalase I overexpression ameliorates renal ischemia-reperfusion injury in rats | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源 | http://purl.org/coar/resource_type/c_46ec | |||||
| タイプ | thesis | |||||
| ID登録 | ||||||
| ID登録 | 10.15083/00002318 | |||||
| ID登録タイプ | JaLC | |||||
| その他のタイトル | ||||||
| その他のタイトル | Glyoxalase I高発現はラットの腎虚血再灌流障害を改善する | |||||
| 著者 |
熊谷, 天哲
× 熊谷, 天哲 |
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| 著者所属 | ||||||
| 著者所属 | 東京大学大学院医学系研究科内科学専攻腎臓内科学 | |||||
| Abstract | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Methylglyoxal (MG), a highly reactive carbonyl compound generated by carbohydrate oxidation and glycolysis, is the major precursor of protein glycation and induces cytotoxicity leading to apoptosis. Although recent studies have emphasized that MG accumulates in not only chronic oxidative stress-related diseases but also acute hypoxic conditions, the pathogenic contribution of MG in acute diseases is unclear. MG is efficiently metabolized by the glyoxalase system, namely glyoxalase I. Ｉ investigated the pathophysiological role of glyoxalase I as an MG detoxifier in rat renal ischemia-reperfusion (I/R) injury. I/R-induced tubulointerstitial injury was associated with a deterioration in renal glyoxalase I activity independent of its cofactor, GSH, as well as an increase in renal MG level. In in vitro studies, knockdown of glyoxalase I by siRNA transfection in rat tubular cells exacerbated cell death by hypoxia-reoxygenation compared to control cells. I also examined whether glyoxalase I overexpression prevented renal I/R damage in rats overexpressing human glyoxalase I with enzyme activity in the kidney 17-fold higher than in wild-type. The histological and functional manifestations of I/R in these rats were significantly ameliorated in association with a decrease in intracellular MG accumulation, oxidative stress and tubular cell apoptosis. In conclusion, glyoxalase I exerts renoprotective effects in renal I/R injury via a reduction in MG accumulation in tubular cells. | |||||
| 書誌情報 | 発行日 2009-03-23 | |||||
| 学位名 | ||||||
| 学位名 | 博士(医学) | |||||
| 学位 | ||||||
| 値 | doctoral | |||||
| 学位分野 | ||||||
| Medical Science (医学) | ||||||
| 学位授与機関 | ||||||
| 学位授与機関名 | University of Tokyo (東京大学) | |||||
| 研究科・専攻 | ||||||
| Department of Internal Medicine, Graduate School of Medicine (医学系研究科内科学専攻) | ||||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2009-03-23 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 甲第24840号 | |||||
| 学位記番号 | ||||||
| 博医第3260号 | ||||||
