Cargando…

SARS-CoV-2 Spike Protein Regulation of Angiotensin Converting Enzyme 2 and Tissue Renin-Angiotensin Systems: Influence of Biologic Sex

Angiotensin converting enzyme 2 (ACE2) is an enzyme that limits activity of the renin-angiotensin system (RAS) and also serves as a receptor for the SARS-CoV-2 Spike (S) protein. Binding of S protein to ACE2 causes internalization which activates local RAS. ACE2 is on the X chromosome and its expres...

Descripción completa

Detalles Bibliográficos
Autores principales: Ensor, Charles M., AlSiraj, Yasir, Shoemaker, Robin, Sturgill, Jamie, Keshavamurthy, Suresh, Gordon, Elizabeth M., Dong, Brittany E., Waters, Christopher, Cassis, Lisa A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452098/
https://www.ncbi.nlm.nih.gov/pubmed/34545369
http://dx.doi.org/10.1101/2021.09.14.460275
_version_ 1784569997304004608
author Ensor, Charles M.
AlSiraj, Yasir
Shoemaker, Robin
Sturgill, Jamie
Keshavamurthy, Suresh
Gordon, Elizabeth M.
Dong, Brittany E.
Waters, Christopher
Cassis, Lisa A
author_facet Ensor, Charles M.
AlSiraj, Yasir
Shoemaker, Robin
Sturgill, Jamie
Keshavamurthy, Suresh
Gordon, Elizabeth M.
Dong, Brittany E.
Waters, Christopher
Cassis, Lisa A
author_sort Ensor, Charles M.
collection PubMed
description Angiotensin converting enzyme 2 (ACE2) is an enzyme that limits activity of the renin-angiotensin system (RAS) and also serves as a receptor for the SARS-CoV-2 Spike (S) protein. Binding of S protein to ACE2 causes internalization which activates local RAS. ACE2 is on the X chromosome and its expression is regulated by sex hormones. In this study, we defined ACE2 mRNA abundance and examined effects of S protein on ACE2 activity and/or angiotensin II (AngII) levels in pivotal tissues (lung, adipose) from male and female mice. In lung, ACE2 mRNA abundance was reduced following gonadectomy (GDX) of male and female mice and was higher in XX than XY mice of the Four Core Genotypes (FCG). Reductions in lung ACE2 mRNA abundance by GDX occurred in XX, but not XY FCG female mice. Lung mRNA abundance of ADAM17 and TMPRSS2, enzymes that shed cell surface ACE2 and facilitate viral cell entry, was reduced by GDX in male but not female mice. For comparison, adipose ACE2 mRNA abundance was higher in female than male mice and higher in XX than XY FCG mice. Adipose ADAM17 mRNA abundance was increased by GDX of male and female mice. S protein reduced ACE2 activity in alveolar type II epithelial cells and 3T3-L1 adipocytes. Administration of S protein to male and female mice increased lung AngII levels and decreased adipose ACE2 activity in male but not female mice. These results demonstrate that sex differences in ACE2 expression levels may impact local RAS following S protein exposures.
format Online
Article
Text
id pubmed-8452098
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Cold Spring Harbor Laboratory
record_format MEDLINE/PubMed
spelling pubmed-84520982021-09-21 SARS-CoV-2 Spike Protein Regulation of Angiotensin Converting Enzyme 2 and Tissue Renin-Angiotensin Systems: Influence of Biologic Sex Ensor, Charles M. AlSiraj, Yasir Shoemaker, Robin Sturgill, Jamie Keshavamurthy, Suresh Gordon, Elizabeth M. Dong, Brittany E. Waters, Christopher Cassis, Lisa A bioRxiv Article Angiotensin converting enzyme 2 (ACE2) is an enzyme that limits activity of the renin-angiotensin system (RAS) and also serves as a receptor for the SARS-CoV-2 Spike (S) protein. Binding of S protein to ACE2 causes internalization which activates local RAS. ACE2 is on the X chromosome and its expression is regulated by sex hormones. In this study, we defined ACE2 mRNA abundance and examined effects of S protein on ACE2 activity and/or angiotensin II (AngII) levels in pivotal tissues (lung, adipose) from male and female mice. In lung, ACE2 mRNA abundance was reduced following gonadectomy (GDX) of male and female mice and was higher in XX than XY mice of the Four Core Genotypes (FCG). Reductions in lung ACE2 mRNA abundance by GDX occurred in XX, but not XY FCG female mice. Lung mRNA abundance of ADAM17 and TMPRSS2, enzymes that shed cell surface ACE2 and facilitate viral cell entry, was reduced by GDX in male but not female mice. For comparison, adipose ACE2 mRNA abundance was higher in female than male mice and higher in XX than XY FCG mice. Adipose ADAM17 mRNA abundance was increased by GDX of male and female mice. S protein reduced ACE2 activity in alveolar type II epithelial cells and 3T3-L1 adipocytes. Administration of S protein to male and female mice increased lung AngII levels and decreased adipose ACE2 activity in male but not female mice. These results demonstrate that sex differences in ACE2 expression levels may impact local RAS following S protein exposures. Cold Spring Harbor Laboratory 2021-09-14 /pmc/articles/PMC8452098/ /pubmed/34545369 http://dx.doi.org/10.1101/2021.09.14.460275 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
spellingShingle Article
Ensor, Charles M.
AlSiraj, Yasir
Shoemaker, Robin
Sturgill, Jamie
Keshavamurthy, Suresh
Gordon, Elizabeth M.
Dong, Brittany E.
Waters, Christopher
Cassis, Lisa A
SARS-CoV-2 Spike Protein Regulation of Angiotensin Converting Enzyme 2 and Tissue Renin-Angiotensin Systems: Influence of Biologic Sex
title SARS-CoV-2 Spike Protein Regulation of Angiotensin Converting Enzyme 2 and Tissue Renin-Angiotensin Systems: Influence of Biologic Sex
title_full SARS-CoV-2 Spike Protein Regulation of Angiotensin Converting Enzyme 2 and Tissue Renin-Angiotensin Systems: Influence of Biologic Sex
title_fullStr SARS-CoV-2 Spike Protein Regulation of Angiotensin Converting Enzyme 2 and Tissue Renin-Angiotensin Systems: Influence of Biologic Sex
title_full_unstemmed SARS-CoV-2 Spike Protein Regulation of Angiotensin Converting Enzyme 2 and Tissue Renin-Angiotensin Systems: Influence of Biologic Sex
title_short SARS-CoV-2 Spike Protein Regulation of Angiotensin Converting Enzyme 2 and Tissue Renin-Angiotensin Systems: Influence of Biologic Sex
title_sort sars-cov-2 spike protein regulation of angiotensin converting enzyme 2 and tissue renin-angiotensin systems: influence of biologic sex
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452098/
https://www.ncbi.nlm.nih.gov/pubmed/34545369
http://dx.doi.org/10.1101/2021.09.14.460275
work_keys_str_mv AT ensorcharlesm sarscov2spikeproteinregulationofangiotensinconvertingenzyme2andtissuereninangiotensinsystemsinfluenceofbiologicsex
AT alsirajyasir sarscov2spikeproteinregulationofangiotensinconvertingenzyme2andtissuereninangiotensinsystemsinfluenceofbiologicsex
AT shoemakerrobin sarscov2spikeproteinregulationofangiotensinconvertingenzyme2andtissuereninangiotensinsystemsinfluenceofbiologicsex
AT sturgilljamie sarscov2spikeproteinregulationofangiotensinconvertingenzyme2andtissuereninangiotensinsystemsinfluenceofbiologicsex
AT keshavamurthysuresh sarscov2spikeproteinregulationofangiotensinconvertingenzyme2andtissuereninangiotensinsystemsinfluenceofbiologicsex
AT gordonelizabethm sarscov2spikeproteinregulationofangiotensinconvertingenzyme2andtissuereninangiotensinsystemsinfluenceofbiologicsex
AT dongbrittanye sarscov2spikeproteinregulationofangiotensinconvertingenzyme2andtissuereninangiotensinsystemsinfluenceofbiologicsex
AT waterschristopher sarscov2spikeproteinregulationofangiotensinconvertingenzyme2andtissuereninangiotensinsystemsinfluenceofbiologicsex
AT cassislisaa sarscov2spikeproteinregulationofangiotensinconvertingenzyme2andtissuereninangiotensinsystemsinfluenceofbiologicsex