Epigallocatechin-3-gallate activates diacylglycerol kinase alpha via a 67 kDa laminin receptor: A possibility of galloylated catechins as functional food to prevent and/or improve diabetic renal dysfunctions

Hayashi, Daiki; Ueda, Shuji; Yamanoue, Minoru; Saito, Naoki; Ashida, Hitoshi; Shirai, Yasuhito

doi:10.1016/j.jff.2015.04.005

Cited by 12 publications

(23 citation statements)

References 25 publications

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“…Interestingly, the abnormal activation of PKCα in DN mediates nephrin endocytosis in podocytes, and the inhibition of abnormal PKCα activation reduces albuminuria in diabetic mice [23,30]. Additionally, we previously demonstrated that DGKα is expressed in podocytes [31]. Therefore, we measured PKCα phosphorylation to investigate the mechanism by which αToc prevented podocyte nephrin loss.…”

Section: Discussionmentioning

confidence: 97%

Amelioration of diabetic nephropathy by oral administration of d-α-tocopherol and its mechanisms

Hayashi

Ueda

Yamanoue

et al. 2018

Bioscience, Biotechnology, and Biochemistry

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Diabetic nephropathy (DN) is a diabetic vascular complication, and abnormal protein kinase C (PKC) activation from increased diacylglycerol (DG) production in diabetic hyperglycemia is one of the causes of DN. Diacylglycerol kinase (DGK) converts DG into phosphatidic acid. In other words, DGK can attenuate PKC activity by reducing the amount of DG. Recently, we reported that intraperitoneally administered d-α-tocopherol (vitamin E, αToc) induces an amelioration of DN in vivo through the activation of DGKα and the prevention of podocyte loss. However, the effect of the oral administration of αToc on DN in mice remains unknown. Here, we evaluated the effect of oral administration of αToc on DN and its molecular mechanism using streptozocin-induced diabetic mice. Consequently, the oral administration of αToc significantly ameliorated the symptoms of DN by preventing the loss of podocytes, and it was revealed that the inhibition of PKCactivity was involved in this amelioration.

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Section: Discussionmentioning

confidence: 97%

Amelioration of diabetic nephropathy by oral administration of d-α-tocopherol and its mechanisms

Hayashi

Ueda

Yamanoue

et al. 2018

Bioscience, Biotechnology, and Biochemistry

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“…In a previous study, we revealed that EGCg activated DGKα via 67LR 22 . To elucidate how EGCg ameliorates DN through DGKα activation, we investigated the signaling pathway, focusing on 67LR.…”

Section: Resultsmentioning

confidence: 90%

“…Observation of GFP-DGKα translocation and calculation of translocation-rate were performed following the previous method 22 . In short, DDT1-MF2 cell or undifferentiated conditionally immortalized human podocyte on glass-bottom dish has transfected the plasmid expressing GFP-DGKα.…”

Section: Methodsmentioning

confidence: 99%

“…Thus far, we have shown that DGKα plays a critical role in the αToc-induced amelioration of DN through in vitro studies and in vivo studies using DGKα-deficient mice 20 , 21 . In addition, our previous study revealed that DGKα is highly expressed in the podocyte 22 . Podocyte is a terminally differentiated cell forming the slit membrane structure in the glomerulus, which functions as a filtration barrier 23 .…”

Section: Introductionmentioning

confidence: 93%

“…Epigallocatechin gallate (EGCg) is a green tea polyphenol and has a chroman ring structure. Furthermore, we found that EGCg activated DGKα through the 67 kDa laminin receptor (67LR), which is known as an EGCg receptor, suggesting the possibility of using EGCg as an agent for treating DN 22 . Indeed, a significant DN ameliorating effect of EGCg was observed in a double-blind human trial, differed from that of the study on αToc and PKCβ inhibitors 27 .…”

Section: Introductionmentioning

confidence: 98%

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The mechanisms of ameliorating effect of a green tea polyphenol on diabetic nephropathy based on diacylglycerol kinase α

Hayashi

Wang

Ueda

et al. 2020

Sci Rep

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Significant efforts have been made to ameliorate diabetic nephropathy (DN) by inhibiting protein kinase C. However, these efforts have not been successful in human trials, suggesting that novel therapeutic strategies are required. Thus far, it has been reported that green tea polyphenol epigallocatechin gallate (EGCg) improved albuminuria in DN in a human trial. Our previous study revealed that activation of diacylglycerol kinase α (DGKα) plays a crucial role in the amelioration of DN and that EGCg activates DGKα. Here, we investigated whether and how DGKα contributes to the amelioration of DN upon stimulation by EGCg by using streptozotocin-induced type 1 diabetic model mice. Our results revealed that EGCg ameliorated albuminuria in DN through DGKα in vivo, and methylated EGCg, which has higher absorption in the plasma improved albuminuria in DN effectively. Additionally, we showed that c-Src mediated EGCg-induced DGKα translocation and colocalized with the 67 kDa laminin receptor, which is an EGCg receptor. Furthermore, EGCg attenuated the loss of podocytes in DN by preventing a decrease in focal adhesion under high glucose conditions. Our results indicate that the DGKα pathway is an attractive therapeutic target and that activating this pathway is a novel strategy for treating DN.

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Protective Role of Alpha-Tocopherol in Diabetic Nephropathy

Hayashi

Shirai

2018

Nutritional and Therapeutic Interventions for Diabetes and Metabolic Syndrome

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Epigallocatechin-3-gallate activates diacylglycerol kinase alpha via a 67 kDa laminin receptor: A possibility of galloylated catechins as functional food to prevent and/or improve diabetic renal dysfunctions

Cited by 12 publications

References 25 publications

Amelioration of diabetic nephropathy by oral administration of d-α-tocopherol and its mechanisms

Amelioration of diabetic nephropathy by oral administration of d-α-tocopherol and its mechanisms

The mechanisms of ameliorating effect of a green tea polyphenol on diabetic nephropathy based on diacylglycerol kinase α

Protective Role of Alpha-Tocopherol in Diabetic Nephropathy

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