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Amino acid sensor GCN2 promotes SARS-CoV-2 receptor ACE2 expression in response to amino acid deprivation

Angiotensin-converting enzyme 2 (ACE2) has been identified as a primary receptor for severe acute respiratory syndrome coronaviruses 2 (SARS-CoV-2). Here, we investigated the expression regulation of ACE2 in enterocytes under amino acid deprivation conditions. In this study, we found that ACE2 expre...

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Autores principales: Hu, Xiaoming, Niu, Yuguo, Luo, Peixiang, Xiao, Fei, Yuan, Feixiang, Yin, Hanrui, Chen, Shanghai, Guo, Feifan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9249868/
https://www.ncbi.nlm.nih.gov/pubmed/35778545
http://dx.doi.org/10.1038/s42003-022-03609-0
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author Hu, Xiaoming
Niu, Yuguo
Luo, Peixiang
Xiao, Fei
Yuan, Feixiang
Yin, Hanrui
Chen, Shanghai
Guo, Feifan
author_facet Hu, Xiaoming
Niu, Yuguo
Luo, Peixiang
Xiao, Fei
Yuan, Feixiang
Yin, Hanrui
Chen, Shanghai
Guo, Feifan
author_sort Hu, Xiaoming
collection PubMed
description Angiotensin-converting enzyme 2 (ACE2) has been identified as a primary receptor for severe acute respiratory syndrome coronaviruses 2 (SARS-CoV-2). Here, we investigated the expression regulation of ACE2 in enterocytes under amino acid deprivation conditions. In this study, we found that ACE2 expression was upregulated upon all or single essential amino acid deprivation in human colonic epithelial CCD841 cells. Furthermore, we found that knockdown of general control nonderepressible 2 (GCN2) reduced intestinal ACE2 mRNA and protein levels in vitro and in vivo. Consistently, we revealed two GCN2 inhibitors, GCN2iB and GCN2-IN-1, downregulated ACE2 protein expression in CCD841 cells. Moreover, we found that increased ACE2 expression in response to leucine deprivation was GCN2 dependent. Through RNA-sequencing analysis, we identified two transcription factors, MAFB and MAFF, positively regulated ACE2 expression under leucine deprivation in CCD841 cells. These findings demonstrate that amino acid deficiency increases ACE2 expression and thereby likely aggravates intestinal SARS-CoV-2 infection.
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spelling pubmed-92498682022-07-03 Amino acid sensor GCN2 promotes SARS-CoV-2 receptor ACE2 expression in response to amino acid deprivation Hu, Xiaoming Niu, Yuguo Luo, Peixiang Xiao, Fei Yuan, Feixiang Yin, Hanrui Chen, Shanghai Guo, Feifan Commun Biol Article Angiotensin-converting enzyme 2 (ACE2) has been identified as a primary receptor for severe acute respiratory syndrome coronaviruses 2 (SARS-CoV-2). Here, we investigated the expression regulation of ACE2 in enterocytes under amino acid deprivation conditions. In this study, we found that ACE2 expression was upregulated upon all or single essential amino acid deprivation in human colonic epithelial CCD841 cells. Furthermore, we found that knockdown of general control nonderepressible 2 (GCN2) reduced intestinal ACE2 mRNA and protein levels in vitro and in vivo. Consistently, we revealed two GCN2 inhibitors, GCN2iB and GCN2-IN-1, downregulated ACE2 protein expression in CCD841 cells. Moreover, we found that increased ACE2 expression in response to leucine deprivation was GCN2 dependent. Through RNA-sequencing analysis, we identified two transcription factors, MAFB and MAFF, positively regulated ACE2 expression under leucine deprivation in CCD841 cells. These findings demonstrate that amino acid deficiency increases ACE2 expression and thereby likely aggravates intestinal SARS-CoV-2 infection. Nature Publishing Group UK 2022-07-01 /pmc/articles/PMC9249868/ /pubmed/35778545 http://dx.doi.org/10.1038/s42003-022-03609-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Hu, Xiaoming
Niu, Yuguo
Luo, Peixiang
Xiao, Fei
Yuan, Feixiang
Yin, Hanrui
Chen, Shanghai
Guo, Feifan
Amino acid sensor GCN2 promotes SARS-CoV-2 receptor ACE2 expression in response to amino acid deprivation
title Amino acid sensor GCN2 promotes SARS-CoV-2 receptor ACE2 expression in response to amino acid deprivation
title_full Amino acid sensor GCN2 promotes SARS-CoV-2 receptor ACE2 expression in response to amino acid deprivation
title_fullStr Amino acid sensor GCN2 promotes SARS-CoV-2 receptor ACE2 expression in response to amino acid deprivation
title_full_unstemmed Amino acid sensor GCN2 promotes SARS-CoV-2 receptor ACE2 expression in response to amino acid deprivation
title_short Amino acid sensor GCN2 promotes SARS-CoV-2 receptor ACE2 expression in response to amino acid deprivation
title_sort amino acid sensor gcn2 promotes sars-cov-2 receptor ace2 expression in response to amino acid deprivation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9249868/
https://www.ncbi.nlm.nih.gov/pubmed/35778545
http://dx.doi.org/10.1038/s42003-022-03609-0
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