High Glucose Stimulates Mineralocorticoid Receptor Transcriptional Activity Through the Protein Kinase C β Signaling

  • Hayashi Takeshi
    Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, School of Medicine, Keio University Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine
  • Shibata Hirotaka
    Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University
  • Kurihara Isao
    Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, School of Medicine, Keio University
  • Yokota Kenichi
    Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, School of Medicine, Keio University
  • Mitsuishi Yuko
    Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, School of Medicine, Keio University
  • Ohashi Kennosuke
    Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine
  • Murai-Takeda Ayano
    Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, School of Medicine, Keio University
  • Jo Rie
    Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, School of Medicine, Keio University
  • Ohyama Takako
    Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, School of Medicine, Keio University
  • Sakamoto Masaya
    Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine
  • Tojo Katsuyoshi
    Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine
  • Tajima Naoko
    Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine
  • Utsunomiya Kazunori
    Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine
  • Itoh Hiroshi
    Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, School of Medicine, Keio University

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説明

<p>Activation of mineralocorticoid receptor (MR) is shown in resistant hypertension including diabetes mellitus. Although protein kinase C (PKC) signaling is involved in the pathogenesis of diabetic complications, an association between PKC and MR is not known. Activation of PKCα and PKCβ by TPA (12-O-Tetradecanoylphorbol 13-acetate) increased MR proteins and its transcriptional activities in HEK293-MR cells. In contrast, a high glucose condition resulted in PKCβ but not PKCα activation, which is associated with elevation of MR protein levels and MR transcriptional activities. Reduction of endogenous PKCβ by siRNA decreased those levels. Interestingly, high glucose did not affect MR mRNA levels, but rather decreased ubiquitination of MR proteins. In db/db mice kidneys, levels of phosphorylated PKCβ2, MR and Sgk-1 proteins were elevated, and the administration of PKC inhibitor reversed these changes compared to db/+ mice. These data suggest that high glucose stimulates PKCβ signaling, which leads to MR stabilization and its transcriptional activities.</p>

収録刊行物

  • International Heart Journal

    International Heart Journal 58 (5), 794-802, 2017

    一般社団法人 インターナショナル・ハート・ジャーナル刊行会

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