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

Data de publicação: 01/01/2024 Data Ahead of Print: 01/07/2024

Autores da FMUP

• Teresa Maria De Jesus Teixeira De Sousa

  Autor

• Fernando José Magro Dias

  Autor

Participantes de fora da FMUP

• Ferreira Duarte, M
• Oliveira, LCG
• Quintas, C
• Dias Pereira, P
• Casarini, DE
• Duarte Ara?jo, M
• Morato, M

Unidades de investigação

• Biomedicina

• Laboratório Associado RISE- Rede de Investigação em Saúde

  

  Investigador

  Fernando Carlos De Landér Schmitt

• RISE-Health

  

  Investigador

  Fernando Carlos De Landér Schmitt

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.

Keywords

• angiotensin-converting enzyme (ACE); angiotensin-converting enzyme 2 (ACE2); colitis; feces; isoforms