ACE2 Activation by Tripeptide IRW (Ile-Arg-Trp) Depends on the G Protein-Coupled Receptor 30 Signaling Cascade.
J Agric Food Chem
; 71(21): 8071-8082, 2023 May 31.
Article
em En
| MEDLINE
| ID: mdl-37199538
ABSTRACT
This study aimed to understand how specific cell-bound receptors influence ACE2 activation by IRW. Our results showed that G protein-coupled receptor 30 (GPR30), a 7-transmembrane domain protein, was involved in IRW-mediated ACE2 increase. IRW treatment (50 µM) significantly increased the GPR30 pool levels (3.2 ± 0.5 folds) (p < 0.001). IRW treatment also boosted the consecutive GEF (guanine nucleotide exchange factor) activity (2.2 ± 0.2 folds) (p < 0.001), and GNB1 levels (2.0 ± 0.5 folds) (p < 0.05), associated with the functional subunits of G proteins, in cells. These results were translated in hypertensive animal studies as well (p < 0.05), indicated by an increase in the aortal levels of GPR30 (p < 0.01); further experiments showed an increase in downstream PIP3/PI3K/Akt pathway activation following IRW treatment. The blockade of GPR30 by an antagonist and siRNA in cells abolished the ACE2-activating ability of IRW, as shown by the depleted levels of ACE2 mRNA (p < 0.001), protein levels in whole cells and membrane, angiotensin (1-7) (p < 0.01), and ACE2 promoter HNF1α (p < 0.05). Finally, the GPR30 blockade in ACE2-overexpressing cells using the antagonist (p < 0.01) and siRNA (p < 0.05) significantly depleted the innate cellular pool of ACE2, thus confirming the relationship between the membrane-bound GPR30 and ACE2. Overall, these results showed that the vasodilatory peptide IRW could activate ACE2 via the membrane-bound receptor GPR30.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfatidilinositol 3-Quinases
/
Enzima de Conversão de Angiotensina 2
Limite:
Animals
Idioma:
En
Revista:
J Agric Food Chem
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Canadá