Angiotensin-converting enzymes 1 and 2 in the feces: presence and catalytic activity in the rat 2,4,6-trinitrobenzene sulfonic acid-induced model of colitis

Author(s)

Ferreira-Duarte, Mariana ; Oliveira, Lilian Caroline Goncalves ; Quintas, Clara ; Dias-Pereira, Patricia ; Sousa, Teresa ; Magro, Fernando ; Casarini, Dulce Elena ; Duarte-Araujo, Margarida ; Morato, Manuela

• Document type: Journal article
• Source: JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY; v. 39, n. 9, p. 10-pg., 2024-07-05.

Abstract

Background and Aim: Inflammatory bowel disease is challenging to diagnose. Fecal biomarkers offer noninvasive solutions. The renin-angiotensin-aldosterone system is implicated in intestinal inflammation. Angiotensin-converting enzyme (ACE) and angiotensin-converting enzyme 2 (ACE2) regulate its activity, but conflicting findings on these enzymes in colitis require further investigation. We aimed to assess ACE and ACE2 presence and activities in the feces, serum, and colon of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced rats. Methods: Colitis was induced in male rats by rectal instillation of a 21% ethanolic TNBS solution. After rats' sacrifice, colonic portions, serum, and feces were collected. ACE and ACE2 presence in the feces was analyzed by western Blot, and colonic and serum enzymes' concentrations were quantified using ELISA kits. ACE activity was assessed using Hippuryl-His-Leu and Z-Phe-His-Leu as substrates. ACE2 activity was assessed using Mca-APK (Dnp) as a substrate in the presence and absence of DX600 (ACE2 inhibitor). Results: An ACE isoform of similar to 70 kDa was found only in the feces of TNBS-induced rats. ACE concentration was higher than that of ACE2 in the serum and the inflamed colon. ACE N-domain activity was higher than that of the C-domain in all matrices. ACE2 activity was higher in the feces of TNBS-induced animals compared to controls. Conclusion: A 70 kDa ACE isoform only detected in the feces of TNBS-induced rats may have translational relevance. ACE N-domain seems to play a significant role in regulating colonic lesions. Further research using human samples is necessary to validate these findings. (AU)

• FAPESP's process: 17/17027-0 - Hormonal systems in renal and cardiovascular diseases: from cell biology to new physiological paradigms with advances for therapeutics
• Grantee: Dulce Elena Casarini
• Support Opportunities: Research Projects - Thematic Grants