Diacylglycerol Kinase alpha is Involved in the Vitamin E-Induced Amelioration of Diabetic Nephropathy in Mice

Abstract 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 e...

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Autores principales:	Daiki Hayashi, Keiko Yagi, Chihong Song, Shuji Ueda, Minoru Yamanoue, Matthew Topham, Toshinobu Suzaki, Naoaki Saito, Noriaki Emoto, Yasuhito Shirai
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/9c1c0ee40faa43709d5cba5f9872558d
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spelling	oai:doaj.org-article:9c1c0ee40faa43709d5cba5f9872558d2021-12-02T15:06:14ZDiacylglycerol Kinase alpha is Involved in the Vitamin E-Induced Amelioration of Diabetic Nephropathy in Mice10.1038/s41598-017-02354-32045-2322https://doaj.org/article/9c1c0ee40faa43709d5cba5f9872558d2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-02354-3https://doaj.org/toc/2045-2322Abstract 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 DGKα isoform in vitro. However, whether DGKα 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 (DGKα+/+) and DGKα–deficient (DGKα−/−) mice in which diabetes was induced by streptozocin. Several symptoms of DN were ameliorated by VtE treatment in the DGKα+/+ mice but not in the DGKα−/− 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 DGKα+/+ mice but not in the DGKα−/− mice. We showed that VtE can ameliorate DN in mice and that DGKα is involved in the VtE-induced amelioration of DN in vivo, suggesting that DGKα is an attractive therapeutic target for DN.Daiki HayashiKeiko YagiChihong SongShuji UedaMinoru YamanoueMatthew TophamToshinobu SuzakiNaoaki SaitoNoriaki EmotoYasuhito ShiraiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daiki Hayashi Keiko Yagi Chihong Song Shuji Ueda Minoru Yamanoue Matthew Topham Toshinobu Suzaki Naoaki Saito Noriaki Emoto Yasuhito Shirai Diacylglycerol Kinase alpha is Involved in the Vitamin E-Induced Amelioration of Diabetic Nephropathy in Mice
description	Abstract 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 DGKα isoform in vitro. However, whether DGKα 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 (DGKα+/+) and DGKα–deficient (DGKα−/−) mice in which diabetes was induced by streptozocin. Several symptoms of DN were ameliorated by VtE treatment in the DGKα+/+ mice but not in the DGKα−/− 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 DGKα+/+ mice but not in the DGKα−/− mice. We showed that VtE can ameliorate DN in mice and that DGKα is involved in the VtE-induced amelioration of DN in vivo, suggesting that DGKα is an attractive therapeutic target for DN.
format	article
author	Daiki Hayashi Keiko Yagi Chihong Song Shuji Ueda Minoru Yamanoue Matthew Topham Toshinobu Suzaki Naoaki Saito Noriaki Emoto Yasuhito Shirai
author_facet	Daiki Hayashi Keiko Yagi Chihong Song Shuji Ueda Minoru Yamanoue Matthew Topham Toshinobu Suzaki Naoaki Saito Noriaki Emoto Yasuhito Shirai
author_sort	Daiki Hayashi
title	Diacylglycerol Kinase alpha is Involved in the Vitamin E-Induced Amelioration of Diabetic Nephropathy in Mice
title_short	Diacylglycerol Kinase alpha is Involved in the Vitamin E-Induced Amelioration of Diabetic Nephropathy in Mice
title_full	Diacylglycerol Kinase alpha is Involved in the Vitamin E-Induced Amelioration of Diabetic Nephropathy in Mice
title_fullStr	Diacylglycerol Kinase alpha is Involved in the Vitamin E-Induced Amelioration of Diabetic Nephropathy in Mice
title_full_unstemmed	Diacylglycerol Kinase alpha is Involved in the Vitamin E-Induced Amelioration of Diabetic Nephropathy in Mice
title_sort	diacylglycerol kinase alpha is involved in the vitamin e-induced amelioration of diabetic nephropathy in mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/9c1c0ee40faa43709d5cba5f9872558d
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Diacylglycerol Kinase alpha is Involved in the Vitamin E-Induced Amelioration of Diabetic Nephropathy in Mice

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