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棕色脂肪组织中肾素活性的特征分析。

Characterization of renin activity in brown adipose tissue.

作者信息

Shenoy U, Cassis L

机构信息

Division of Pharmacology and Experimental Therapeutics, College of Pharmacy, University of Kentucky, Lexington 40536, USA.

出版信息

Am J Physiol. 1997 Mar;272(3 Pt 1):C989-99. doi: 10.1152/ajpcell.1997.272.3.C989.

Abstract

Angiotensin (ANG) II plays a vital role in blood pressure regulation and body fluid homeostasis. Although many peripheral tissues synthesize components of the renin-ANG system, very few synthesize all of the major components involved in the generation ofANG II. This study used interscapular brown adipose tissue (ISBAT) as a model system to evaluate the mechanism of ANG II generation in an extrarenal tissue. Polymerase chain reaction analysis of DNA from ISBAT demonstrated angiotensinogen gene expression; however, renin gene expression was not detected. Renin activity that was not completely derived from the residual blood pool was detected in ISBAT homogenates. Kinetic parameters for renin activity were similar in ISBAT and adrenal gland. Renin activity was partially inhibited by anti-renin antibody and completely inhibited by a specific rat renin inhibitor. Bilateral nephrectomy did not decrease renin activity in ISBAT. Western blot analysis, employing two species-specific renin antibodies, indicated the presence of a variety of isoforms of renin in ISBAT. The presence of renin activity in isolated brown adipocytes demonstrated that the enzyme is localized to adipocytes. The release of immunoreactive ANG peptides from ISBAT slices over 3 h indicated de novo synthesis. These studies support the existence of a local renin-ANG system in ISBAT and suggest involvement of renin in the formation of ANG II.

摘要

血管紧张素(ANG)II在血压调节和体液平衡中起着至关重要的作用。尽管许多外周组织能合成肾素-ANG系统的成分,但很少有组织能合成参与ANG II生成的所有主要成分。本研究以肩胛间棕色脂肪组织(ISBAT)作为模型系统,评估肾外组织中ANG II的生成机制。对ISBAT的DNA进行聚合酶链反应分析显示有血管紧张素原基因表达;然而,未检测到肾素基因表达。在ISBAT匀浆中检测到并非完全来源于残留血池的肾素活性。ISBAT和肾上腺中肾素活性的动力学参数相似。肾素活性部分被抗肾素抗体抑制,被一种特异性大鼠肾素抑制剂完全抑制。双侧肾切除并未降低ISBAT中的肾素活性。使用两种种属特异性肾素抗体进行的蛋白质印迹分析表明,ISBAT中存在多种肾素同工型。分离的棕色脂肪细胞中存在肾素活性,表明该酶定位于脂肪细胞。ISBAT切片在3小时内释放免疫反应性ANG肽表明有从头合成。这些研究支持ISBAT中存在局部肾素-ANG系统,并提示肾素参与ANG II的形成。

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