PDZK1 improves ventricular remodeling in hypertensive rats by regulating the stability of the Mas receptor

IF 3 3区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Amino Acids Pub Date : 2023-09-11 DOI:10.1007/s00726-023-03331-z

Jinyu Chi, Wanlin Li, Yang Xu, Xiuzhi Li, Xiaohui Zhang, Zhiyu Shi, Chunnan Liu, Wenxiu Liu, Meng Zhao, Yan Meng, Dechao Zhao

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Abstract

Ventricular remodeling is one of the main causes of mortality from heart failure due to hypertension. Exploring its mechanism and finding therapeutic targets have become urgent scientific problems to be solved. A number of studies have shown that Mas, as an Ang-(1-7) specific receptor, was significantly reduced in myocardial tissue of rats undergoing hypertensive ventricular remodeling. It has been reported that Mas receptor levels are significantly downregulated in myocardium undergoing ventricular remodeling, but studies focused on intracellular and post-translational modifications of Mas are lacking. The results of this research are as follows: (1) PDZK1 interacts with the carboxyl terminus of Mas through its PDZ1 domain; (2) the expression of PDZK1 and Mas is decreased in rats undergoing hypertensive ventricular remodeling, and PDZK1 upregulation can ameliorate hypertensive myocardial fibrosis and myocardial hypertrophy; (3) PDZK1 enhances the stability of Mas protein through the proteasome pathway, and the proteasome inhibitor MG132 promotes hypertensive ventricular remodeling. PDZK1 improves ventricular remodeling in hypertensive rats by regulating Mas receptor stability. This study provides a scientific basis for the prevention and treatment of ventricular remodeling.

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PDZK1通过调节Mas受体的稳定性改善高血压大鼠心室重构。

心室重构是高血压引起心力衰竭死亡的主要原因之一。探索其机制和寻找治疗靶点已成为亟待解决的科学问题。大量研究表明，Mas作为一种Ang-(1-7)特异性受体，在高血压心室重构大鼠心肌组织中显著减少。据报道，在心室重构的心肌中，Mas受体水平显著下调，但缺乏对Mas细胞内和翻译后修饰的研究。本研究结果如下:(1)PDZK1通过其PDZ1结构域与Mas的羧基端相互作用;(2)高血压心室重构大鼠PDZK1和Mas表达降低，PDZK1上调可改善高血压心肌纤维化和心肌肥厚;(3) PDZK1通过蛋白酶体途径增强Mas蛋白的稳定性，蛋白酶体抑制剂MG132促进高血压心室重构。PDZK1通过调节Mas受体稳定性改善高血压大鼠心室重构。本研究为预防和治疗心室重构提供了科学依据。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Amino Acids 生物-生化与分子生物学

CiteScore

6.40

自引率

5.70%

发文量

审稿时长

2.2 months

期刊介绍： Amino Acids publishes contributions from all fields of amino acid and protein research: analysis, separation, synthesis, biosynthesis, cross linking amino acids, racemization/enantiomers, modification of amino acids as phosphorylation, methylation, acetylation, glycosylation and nonenzymatic glycosylation, new roles for amino acids in physiology and pathophysiology, biology, amino acid analogues and derivatives, polyamines, radiated amino acids, peptides, stable isotopes and isotopes of amino acids. Applications in medicine, food chemistry, nutrition, gastroenterology, nephrology, neurochemistry, pharmacology, excitatory amino acids are just some of the topics covered. Fields of interest include: Biochemistry, food chemistry, nutrition, neurology, psychiatry, pharmacology, nephrology, gastroenterology, microbiology