A model for COVID-19-induced dysregulation of ACE2 shedding by ADAM17.

Autor: Healy EF; Department of Chemistry, St. Edward's University, Austin, TX 78704, USA. Electronic address: healy@stedwards.edu., Lilic M; Department of Chemistry, St. Edward's University, Austin, TX 78704, USA.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2021 Oct 08; Vol. 573, pp. 158-163. Date of Electronic Publication: 2021 Aug 15.
DOI: 10.1016/j.bbrc.2021.08.040
Abstrakt: 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 protease TMPRSS2 is necessary for virion internalization. Complicating the issue is the observation that circulating ACE2 can also bind to the virus effectively blocking attachment to the membrane-bound receptor. This work investigates the possibility that the inflammatory response to coronavirus infection can abrogate shedding by ADAM17, thereby favoring cleavage by TMPRSS2 and thus cell entry by the virion.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2021 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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