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

Abstract

To develop a functional food for improvement and/or prevention of diabetic nephropathy, we investigated whether catechins can activate DGKα, which is involved in the vitamin E-induced improvement of diabetic renal dysfunction. Among the catechins tested, (-)-epicatechin-3-gallate, (-)-epigallocatechin-3-gallate (EGCg), (-)-catechin-3-gallate and (-)-gallocatechin-3-gallate induced DGKα translocation from the cytoplasm to the plasma membrane, which is an index of DGKα activation. In contrast, (-)-epicatechin, (-)-epigallocatechin and gallic acid did not induce the translocation. Among the four galloylated catechins, EGCg was most effective, dose-dependent and subtype-specific among type I DGKs. Importantly, EGCg did indeed up-regulate DGKα activity. In addition, we found that a 67 kDa laminin receptor (67LR) mediates the EGCg-induced activation of DGKα, and both 67LR and DGKα are expressed in podocyte among glomerular cells. Finally, the EGCg-induced translocation of DGKα was confirmed in cultured podocytes. Thus, EGCg activates DGKα via 67LR, providing the possibility that EGCg may improve and/or prevent diabetic renal dysfunction.

Keywords

• Diacylglycerol kinase
• 67 kDa laminin receptor
• Catechin
• Vitamin E
• Diabetic renal dysfunction
• Protein kinase C