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SARS-CoV-2 刺突蛋白增强血管紧张素转化酶 2 的羧肽酶活性。

SARS-CoV-2 Spike Protein Enhances Carboxypeptidase Activity of Angiotensin-Converting Enzyme 2.

机构信息

Department of Molecular Biology, Instituto Nacional de Cardiología "Ignacio Chávez", Mexico City 14080, Mexico.

Carrera de Médico Cirujano, Facultad de Estudios Superiores Iztacala, Universidad Nacional Autónoma de México, Mexico City 54090, Mexico.

出版信息

Int J Mol Sci. 2024 Jun 6;25(11):6276. doi: 10.3390/ijms25116276.

DOI:10.3390/ijms25116276
PMID:38892464
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11172802/
Abstract

In this study, we investigated whether severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) spike protein may modify angiotensin-converting enzyme 2 (ACE2) activity in the plasma, heart, kidney, liver, lung, and six brain regions (amygdala, brain stem, cortex, hippocampus, hypothalamus, and striatum) of diabetic and hypertensive rats. We determine ACE2 activity in the plasma and lysates of heart, kidney, liver, lung, and six brain regions. MLN-4760 inhibits ACE2 activity in the plasma and all organs. On the other hand, soluble ACE2 (sACE2) activity increased in the plasma of diabetic rats, and there was no change in the plasma of hypertensive rats. ACE2 activity was augmented in the liver, brain stem, and striatum, while it decreased in the kidney, amygdala, cortex, and hippocampus of diabetic rats. ACE2 activity increased in the kidney, liver, and lung, while it decreased in the heart, amygdala, cortex, and hypothalamus of hypertensive rats. We measured the ACE2 content via enzyme-linked immunosorbent assay and found that ACE2 protein levels increased in the heart, while it decreased in the plasma, kidney, brain stem, cortex, hippocampus, hypothalamus, and striatum of diabetic rats. ACE2 protein levels decreased in the brain stem, cortex, hippocampus, and hypothalamus of hypertensive rats. Our data showed that the spike protein enhanced ACE2 activity in the liver and lungs of diabetic rats, as well as in the heart and three of the brain regions (cortex, hypothalamus, and striatum) of hypertensive rats.

摘要

在这项研究中，我们研究了严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）刺突蛋白是否可能改变糖尿病和高血压大鼠血浆、心脏、肾脏、肝脏、肺和六个脑区（杏仁核、脑干、皮质、海马、下丘脑和纹状体）中血管紧张素转换酶 2（ACE2）的活性。我们测定了血浆和心脏、肾脏、肝脏、肺和六个脑区的裂解物中的 ACE2 活性。MLN-4760 抑制了血浆和所有器官中的 ACE2 活性。另一方面，糖尿病大鼠血浆中的可溶性 ACE2（sACE2）活性增加，高血压大鼠血浆中的 sACE2 活性没有变化。ACE2 活性在糖尿病大鼠的肝脏、脑干和纹状体中增加，而在肾脏、杏仁核、皮质和海马中减少。ACE2 活性在糖尿病大鼠的肾脏、肝脏和肺中增加，而在心脏、杏仁核、皮质和下丘脑减少。我们通过酶联免疫吸附测定法测量了 ACE2 的含量，发现 ACE2 蛋白水平在心脏中增加，而在糖尿病大鼠的血浆、肾脏、脑干、皮质、海马、下丘脑和纹状体中减少。ACE2 蛋白水平在高血压大鼠的脑干、皮质、海马和下丘脑减少。我们的数据表明，刺突蛋白增强了糖尿病大鼠肝脏和肺以及高血压大鼠心脏和三个脑区（皮质、下丘脑和纹状体）中 ACE2 的活性。

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