| Full text | |
| Author(s): |
Leite, A. P. O.
[1, 2]
;
Aragao, Danielle S.
[1]
;
Nogueira, Marie D.
[1]
;
Pereira, Renata O.
[1, 2]
;
Jara, Zaira P.
[1, 3]
;
Fiorino, Patricia
[2]
;
Casarini, Dulce E.
[1]
;
Farah, Vera
[1, 2]
Total Authors: 8
|
| Affiliation: | [1] Univ Fed Sao Paulo, Dept Med, Escola Paulista Med, Disciplina Nefrol, Sao Paulo - Brazil
[2] Univ Presbiteriana Mackenzie, Ctr Ciencia Saude & Biol, Lab Renal Cardiovasc & Fisiofarmacol Metabol, Sao Paulo - Brazil
[3] Cleveland Clin, Lerner Res Inst, Dept Mol Cardiol, Cleveland, OH 44106 - USA
Total Affiliations: 3
|
| Document type: | Journal article |
| Source: | Journal of Cellular Physiology; v. 234, n. 12, p. 22809-22818, DEC 2019. |
| Web of Science Citations: | 0 |
| Abstract | |
Diabetes mellitus and its complications have become a major health concern in Western countries. Increased activity of the intrarenal renin-angiotensin system (RAS) contributes to diabetic nephropathy (DN). We previously reported that in mesangial cells, the high glucose concentration (HG) leads to upregulation of angiotensin-converting enzyme (ACE) messenger RNA, suggesting that ACE was modulated by angiotensin II (Ang II) release. However, this relation in the collecting duct has not yet been studied. We, therefore, aimed to evaluate RAS modulation in inner medullary collecting duct cells (IMCD) exposed to HG. The IMCD were divided into normal glucose (5mM D-glucose, NG), high glucose (30mM, HG), and mannitol (30mM, M) groups. The cells were cultured 48hr in their respective media. The intracellular and extracellular ACE activity was measured using hippuryl-His-Leu as substrate via a fluorimetric assay and expression was analyzed using western blot analysis. ACE activity, intracellular (27%) and extracellular (22%), was significantly lower in the HG group than in NG and M. ACE2 activity and Ang 1-7 levels were higher in the intracellular compartment. Our data suggest that the HG cannot modify ACE synthesis in IMCD cells but can modulate its activity. The decrease in ACE activity may result in decreased levels of Ang II to protect the IMCD against proliferative and inflammatory deleterious effects of this peptide. Conversely, the increase of ACE2 generating high levels of Ang 1-7, a vasodilator peptide, suggesting that this peptide can induce glucose uptake and protect cells against oxidative stress, which can elicit insulin resistance. (AU) | |
| FAPESP's process: | 10/51904-9 - Renin angiotensin and kallikrein kinin systems in hypertension, obesity, diabetes, desnutrition and sepsis: molecular, cellular and physiopathologic mechanisms |
| Grantee: | Dulce Elena Casarini |
| Support Opportunities: | Research Projects - Thematic Grants |