High Glucose Stimulates Mineralocorticoid Receptor Transcriptional Activity Through the Protein Kinase C β Signaling
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- 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
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- Shibata Hirotaka
- Department of Endocrinology, Metabolism, Rheumatology and Nephrology, Faculty of Medicine, Oita University
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- Kurihara Isao
- Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, School of Medicine, Keio University
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- Yokota Kenichi
- Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, School of Medicine, Keio University
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- Mitsuishi Yuko
- Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, School of Medicine, Keio University
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- Ohashi Kennosuke
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine
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- Murai-Takeda Ayano
- Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, School of Medicine, Keio University
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- Jo Rie
- Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, School of Medicine, Keio University
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- Ohyama Takako
- Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, School of Medicine, Keio University
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- Sakamoto Masaya
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine
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- Tojo Katsuyoshi
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine
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- Tajima Naoko
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine
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- Utsunomiya Kazunori
- Division of Diabetes, Metabolism and Endocrinology, Department of Internal Medicine, Jikei University School of Medicine
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- Itoh Hiroshi
- Division of Endocrinology, Metabolism and Nephrology, Department of Internal Medicine, School of Medicine, Keio University
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Description
<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>
Journal
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- International Heart Journal
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International Heart Journal 58 (5), 794-802, 2017
International Heart Journal Association
