SARS-CoV-2 spike protein increases angiotensin converting enzyme-2 expression and promotes an increase in glucose uptake in endothelial cells

IF 1.1 4区 医学 Q4 VIROLOGY Acta virologica Pub Date : 2024-03-04 DOI:10.3389/av.2024.12136
Mariana F. Campos, Larissa E. C. Constant, D. E. Teixeira, Rodrigo P. Silva-Aguiar, Patrícia R. M. Rocco, Ronaldo Mohana-Borges, Gilda G. Leitão, Celso Caruso-Neves, Suzana G. Leitão, D. Allonso
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Abstract

Coronavirus Disease 2019 (COVID-19) pandemic led to 7 million deaths and more than 770 million confirmed cases worldwide. The Spike glycoprotein (SP) is responsible for recognizing and binding to angiotensin converting enzyme-2 (ACE-2) in the host cell membrane and seems to modulate host cellular signaling pathways. Here, we investigate the effects of SP (stabilized in prefusion conformation) in human umbilical vein endothelial cells (HUVEC-C) lineage on the ACE-2 expression profile and in cell glucose metabolism. Our data indicate that SP binds to ACE-2, is internalized by HUVEC-C cells, and positively modulates ACE-2 expression. In addition, SP alone induces a transient increase in glucose uptake and a decrease in lactate production, characterizing itself as a metabolic regulating protein. The present study is the first to demonstrate that SP induces a slight change in cell metabolism, promotes the overexpression of ACE-2 and its increased availability in the membrane of endothelial cells in a time-dependent fashion.
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SARS-CoV-2 穗状病毒蛋白可增加血管紧张素转换酶-2 的表达,并促进内皮细胞摄取葡萄糖的增加
2019 年冠状病毒病(COVID-19)大流行导致全球 700 万人死亡,确诊病例超过 7.7 亿例。穗状糖蛋白(SP)负责识别宿主细胞膜上的血管紧张素转换酶-2(ACE-2)并与之结合,似乎能调节宿主细胞信号通路。在此,我们研究了人脐静脉内皮细胞(HUVEC-C)系中 SP(稳定在预融合构象)对 ACE-2 表达谱和细胞葡萄糖代谢的影响。我们的数据表明,SP 与 ACE-2 结合,被 HUVEC-C 细胞内化,并积极调节 ACE-2 的表达。此外,SP 还能诱导葡萄糖摄取的短暂增加和乳酸生成的减少,从而使其成为一种代谢调节蛋白。本研究首次证明,SP 可诱导细胞代谢发生轻微变化,促进 ACE-2 的过表达,并以时间依赖的方式增加其在内皮细胞膜中的可用性。
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来源期刊
Acta virologica
Acta virologica 医学-病毒学
CiteScore
3.10
自引率
11.80%
发文量
43
审稿时长
>12 weeks
期刊介绍: Acta virologica is an international journal of predominantly molecular and cellular virology. Acta virologica aims to publish papers reporting original results of fundamental and applied research mainly on human, animal and plant viruses at cellular and molecular level. As a matter of tradition, also rickettsiae are included. Areas of interest are virus structure and morphology, molecular biology of virus-cell interactions, molecular genetics of viruses, pathogenesis of viral diseases, viral immunology, vaccines, antiviral drugs and viral diagnostics.
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