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Abstract: FR-PO592

The Novel Role of 14-3-3 Gamma in the Pathogenesis of Deoxycorticosterone Acetate Salt Hypertensive Mouse Model

Session Information

Category: Fluid and Electrolytes

  • 901 Fluid and Electrolytes: Basic


  • Li, Ruidian, Emory University School of Medicine, Atlanta, Georgia, United States
  • Feng, Xiuyan, LSU Shreveport , Shreveport, Louisiana, United States
  • Luo, Tongwang, Emory University, Atlanta, Georgia, United States
  • Li, Chunmei, Emory University, Atlanta, Georgia, United States
  • Bi, Ye, Emory University, Atlanta, Georgia, United States
  • Huang, Yufeng, Fibrosis Research Laboratory, Salt Lake City, Utah, United States
  • Cai, Hui, Emory University School of Medicine, Atlanta, Georgia, United States

Sodium chloride cotransporter (NCC) plays a key role in the regulation of blood pressure and electrolyte homeostasis. 14-3-3 γ belongs to a family of multifunction regulatory proteins. Previous data have shown that 14-3-3 proteins regulate renal ion channel and transporter such as ENaC. Our preliminary data showed that 14-3-3γ inhibits NCC. Thus, we hypothesized that 14-3-3 γ plays a role in affecting blood pressure regulation through NCC. The purpose of this study is to investigate the role of 14-3-3 γ in NCC regulation in DOCA-salt hypertensive mouse model.


DOCA salt mouse, western blot analysis, cell culture, siRNA knock-down experiments, and tail-cuff blood pressure (BP) measurement were used in this study.


To determine whether 14-3-3 γ has a role in the pathogenesis of hypertension, we first established the DOCA salt hypertensive mouse model. Systolic blood pressure was significantly higher in DOCA salt hypertensive mice than that in control mice (148 ± 25 vs 119 ± 20, p < 0.01, n=4). Western blot analysis from the kidney tissues harvested from these mice showed that 14-3-3 γ protein abundance was significantly reduced in DOCA salt hypertensive mice compared to the control mice group (100 ± 11.3 % vs 58.2 ± 11.8 %, p < 0.01, n=4). Total NCC and phospho-NCC were significantly increased in DOCA salt group compared to the control group (1.0 ± 0.12 vs 1.4 ± 0.25; 1.0 ± 0.17 vs 1.34 ± 0.10, respectively, p < 0.05, n=4). ERK 1/2 phosphorylation was significantly reduced in DOCA salt group compared to the control group. To further investigate the role of ERK 1/2 signaling pathway in the 14-3-3 γ-mediated NCC regulation, we performed the 14-3-3 gamma knock-down experiments in Cos-7 cells transfected with 14-3-3 γ siRNA and NCC. Knocking down 14-3-3 γ expression significantly increased total NCC protein expression while reducing ERK 1/2 phosphorylation. Overexpression of 14-3-3γ significantly reduced NCC protein expression while enhancing ERK 1/2 phosphorylation. In the presence of knock-down ERK 1/2, 14-3-3 γ-mediated inhibition of NCC was reversed.


Taken all data together, we concluded that 14-3-3 γ plays an important role in NCC regulation through ERK 1/2-mediated signaling pathway in DOCA salt hypertensive mouse model, which provides a novel mechanism underlying pathogenesis of DOCA salt hypertension.


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