学術雑誌論文 Diacylglycerol Kinase alpha is Involved in the Vitamin E-Induced Amelioration of Diabetic Nephropathy in Mice

Hayashi, Daiki  ,  Yagi, Keiko  ,  Song, Chihong  ,  Ueda, Shuji  ,  Yamanoue, Minoru  ,  Topham, Matthew  ,  Suzaki, Toshinobu  ,  Saito, Naoaki  ,  Emoto, Noriaki  ,  Shirai, Yasuhito

7p.2597 , 2017-06-01 , Nature Publishing Group
ISSN:2045232220452322
内容記述
Diabetic nephropathy (DN) is one of vascular complications of diabetes and is caused by abnormal protein kinase C activation as a result of increased diacylglycerol (DG) production in diabetic hyperglycaemia. Diacylglycerol kinase (DGK) converts DG into phosphatidic acid. Therefore, it is expected that the activation of DGK would ameliorate DN. Indeed, it has been reported that vitamin E (VtE) ameliorates DN in rat by activating DGK, and we recently reported that VtE specifically activates DGK alpha isoform in vitro. However, whether DGK alpha is involved in the VtE-induced amelioration of DN in vivo remains unknown. Therefore, we investigated the VtE-induced amelioration of DN in wild-type (DGK alpha(+/+)) and DGK alpha-deficient (DGK alpha(-/-)) mice in which diabetes was induced by streptozocin. Several symptoms of DN were ameliorated by VtE treatment in the DGK alpha(+/+) mice but not in the DGK alpha(-/-) mice. Moreover, transmission electron microscopy of glomeruli and immunofluorescent staining of glomerular epithelial cells (podocytes) indicated that VtE ameliorates podocyte pathology and prevents podocyte loss in the DGK alpha(+/+) mice but not in the DGK alpha(-/-) mice. We showed that VtE can ameliorate DN in mice and that DGK alpha is involved in the VtE-induced amelioration of DN in vivo, suggesting that DGK alpha is an attractive therapeutic target for DN.
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http://www.lib.kobe-u.ac.jp/repository/90004196.pdf

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