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

Abstract:

: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.

journal_name

Int Heart J

authors

Hayashi T,Shibata H,Kurihara I,Yokota K,Mitsuishi Y,Ohashi K,Murai-Takeda A,Jo R,Ohyama T,Sakamoto M,Tojo K,Tajima N,Utsunomiya K,Itoh H

doi

10.1536/ihj.16-649

subject

Has Abstract

pub_date

2017-10-21 00:00:00

pages

794-802

issue

5

eissn

1349-2365

issn

1349-3299

journal_volume

58

pub_type

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