A model for COVID-19-induced dysregulation of ACE2 shedding by ADAM17.
Biochem Biophys Res Commun
; 573: 158-163, 2021 10 08.
Article
in English
| MEDLINE | ID: covidwho-1446454
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 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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
HSP20 Heat-Shock Proteins
/
Host-Pathogen Interactions
/
ADAM17 Protein
/
Angiotensin-Converting Enzyme 2
/
SARS-CoV-2
Type of study:
Observational study
/
Prognostic study
Limits:
Humans
Language:
English
Journal:
Biochem Biophys Res Commun
Year:
2021
Document Type:
Article
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