2021
DOI: 10.1016/j.bbrc.2021.08.040
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A model for COVID-19-induced dysregulation of ACE2 shedding by ADAM17

Abstract: The angiotensin Converting Enzyme 2 (ACE2) receptor is a key component of the renin-angiotensin-aldesterone system (RAAS) that mediates numerous effects in the cardiovascular system. It is also the cellular point of contact for the coronavirus spike protein. Cleavage of the receptor is both important to its physiological function as well as being necessary for cell entry by the virus. Shedding of ACE2 by the metalloprotease ADAM17 releases a catalytically active soluble form of ACE2, but cleavage by the serine… Show more

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Cited by 21 publications
(13 citation statements)
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“…ADAM17 (a disintegrin and metalloproteinase domain 17) is engaged in the cleavage and release of ACE2 ( 52 ) and its upregulation was associate with an increase extracellular release of ACE2 in its soluble form (sACE2). Circulating sACE2 can bind to the SARS-CoV-2 virus effectively, acting as soluble decoy and blocking attachment to the membrane-bound receptor and virus entry ( 53 , 54 ). An increase in heparanase secretion and of Has-1, was also demonstrated after OM-85 treatment (respectively at 1:50, and 1:100 or at 1:50 dilutions) ( 49 ).…”
Section: Anti-viral Activities Of Om-85: In Vitro ...mentioning
confidence: 99%
“…ADAM17 (a disintegrin and metalloproteinase domain 17) is engaged in the cleavage and release of ACE2 ( 52 ) and its upregulation was associate with an increase extracellular release of ACE2 in its soluble form (sACE2). Circulating sACE2 can bind to the SARS-CoV-2 virus effectively, acting as soluble decoy and blocking attachment to the membrane-bound receptor and virus entry ( 53 , 54 ). An increase in heparanase secretion and of Has-1, was also demonstrated after OM-85 treatment (respectively at 1:50, and 1:100 or at 1:50 dilutions) ( 49 ).…”
Section: Anti-viral Activities Of Om-85: In Vitro ...mentioning
confidence: 99%
“…A disintegrin and metallopeptidase domain 17 (ADAM17)/tumor necrosis factor α-converting enzyme cleaves ACE2 off the cell surface, generating circulating ACE2, an enzyme with an active ectodomain (cACE2)[ 27 ]. In 2005, Lambert et al [ 28 ] validated the ectodomain shedding of endogenously produced ACE2 in Huh7 cells and heterologously synthesized ACE2 in HEK293 cells.…”
Section: Circulating Ace2 In Health and Diseasesmentioning
confidence: 99%
“…As a type-I multidomain transmembrane protein, the pro-domain of ADAM17 possesses catalytic activity (10). Once the predomain is hydrolyzed, ADAM17 participates in the hydrolysis and abscission of various extracellular functional regions of proteins, such as ACE2 (11). Increased ACE2 shedding triggers enhanced viral infection.…”
Section: Introductionmentioning
confidence: 99%