Tocotrienols activate diacylglycerol kinase a via 67 KDa laminin receptor

Background: Diabetes is a significant social issue. Controlling diabetic complications such as nephropathy is crucial for the quality of life (QOL) of diabetic patients. The abnormal activation of protein kinase C (PKC) through increased diacylglycerol levels (DG) due to hyperglycemia is a common mechanism that causes diabetic complications. Diacylglycerol kinase (DGK) can attenuate PKC activity by converting DG to phosphatidic acid. Thus far, d-α-tocopherol (αToc) treatment has been shown to prevent early changes of diabetic renal dysfunctions by activating DGKα via the 67KDa laminin receptor. Vitamin E is classified into tocopherols (Toc) and tocotrienols (T3) with four derivatives: α, β, γα, β, γ, and δ. We have found that all Tocs induced the translocation of DGKα. However, it remains unclear if T3s also induced translocation of DGKα. Objective: The objective of the study was to investigate the relationship between tocotrienols (T3s) and induced translocation of DGKα, while exploring the mechanism underlying T3s-induced translocation of DGKα. Results: Similarly to a-tocopherol, α-T3 binds to 67LR, resulting in the induction of a translocation of DGK. As well as α- T3, β, γ, δ, and α Tocs induced translocation of DGK. Conclusion: αT3, like αToc, activates DGKα by binding to Leu58 and Trp176 in 67LR. It means 67LR may be important for the functions of T3s, especially the non-oxidant effects of T3s. Keywords: catechins, diabetic nephropathy, diacylglycerol kinase, vitamin E