Specific translocation and activation of DGKα by d-αtocopherol

D-αtocopherol (VitE) treatment is reported to improve the diabetic renal dysfunctions through inhibition of protein kinase C. The details are not clear although it is considered that the VitE- induced activation of diacyiglycerol kinase (DGK) and the anti-oxidization action of VitE are important. We...

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Bibliographic Details
Published in:Journal of Pharmacological Sciences 2004, Vol.94 (suppl.2), p.126-126
Main Authors: Rika Takenaka, Yasuhito Shirai, Norio Sakai, Noaki Saito
Format: Article
Language:Japanese
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Summary:D-αtocopherol (VitE) treatment is reported to improve the diabetic renal dysfunctions through inhibition of protein kinase C. The details are not clear although it is considered that the VitE- induced activation of diacyiglycerol kinase (DGK) and the anti-oxidization action of VitE are important. We analyzed the response of GFP-tagged DGKα, β, γ, δ and ε to VitE and the derivatives under confocal laser microscopy. Only DGKα translocated from the cytosol to the plasma membrane and activated in response to all stimulations, indicating the importance of VitE framework for the activation. The translocation of DGKα by VitE was inhibited by the pretreatment with tyrosine kinase inhibitors, suggesting that tyrosine phosphorylation was involved in the translocation of DGKα by VitE. The VitE-induced translocation of DGKα was abolished by the point mutation of C1A or C1B domain, demonstrating involvement of the C1 domain in the translocation. These findings suggest that the VitE induces translocation and activation of DGKα, via C1 domain and tyrosine phosphorylation, plays an important role to improvement of diabetic nephropathy.
ISSN:1347-8613