Uptake and metabolism of the novel peptide angiotensin-(1-12) by neonatal cardiac myocytes.
Angiotensin-(1-12) [Ang-(1-12)] functions as an endogenous substrate for the productions of Ang II and Ang-(1-7) by a non-renin dependent mechanism. This study evaluated whether Ang-(1-12) is incorporated by neonatal cardiac myocytes and the enzymatic pathways of ¹²⁵I-Ang-(1-12) metabolism in the ca...
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doaj-0bbbb380de8f4fc0b447d5b0c421c22b2020-11-24T21:33:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0161e1575910.1371/journal.pone.0015759Uptake and metabolism of the novel peptide angiotensin-(1-12) by neonatal cardiac myocytes.Sarfaraz AhmadJasmina VaragicBrian M WestwoodMark C ChappellCarlos M FerrarioAngiotensin-(1-12) [Ang-(1-12)] functions as an endogenous substrate for the productions of Ang II and Ang-(1-7) by a non-renin dependent mechanism. This study evaluated whether Ang-(1-12) is incorporated by neonatal cardiac myocytes and the enzymatic pathways of ¹²⁵I-Ang-(1-12) metabolism in the cardiac myocyte medium from WKY and SHR rats.The degradation of ¹²⁵I-Ang-(1-12) (1 nmol/L) in the cultured medium of these cardiac myocytes was evaluated in the presence and absence of inhibitors for angiotensin converting enzymes 1 and 2, neprilysin and chymase. In both strains uptake of ¹²⁵I-Ang-(1-12) by myocytes occurred in a time-dependent fashion. Uptake of intact Ang-(1-12) was significantly greater in cardiac myocytes of SHR as compared to WKY. In the absence of renin angiotensin system (RAS) enzymes inhibitors the hydrolysis of labeled Ang-(1-12) and the subsequent generation of smaller Ang peptides from Ang-(1-12) was significantly greater in SHR compared to WKY controls. ¹²⁵I-Ang-(1-12) degradation into smaller Ang peptides fragments was significantly inhibited (90% in WKY and 71% in SHR) in the presence of all RAS enzymes inhibitors. Further analysis of peptide fractions generated through the incubation of Ang-(1-12) in the myocyte medium demonstrated a predominant hydrolytic effect of angiotensin converting enzyme and neprilysin in WKY and an additional role for chymase in SHR.These studies demonstrate that neonatal myocytes sequester angiotensin-(1-12) and revealed the enzymes involved in the conversion of the dodecapeptide substrate to biologically active angiotensin peptides.http://europepmc.org/articles/PMC3018413?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sarfaraz Ahmad Jasmina Varagic Brian M Westwood Mark C Chappell Carlos M Ferrario |
spellingShingle |
Sarfaraz Ahmad Jasmina Varagic Brian M Westwood Mark C Chappell Carlos M Ferrario Uptake and metabolism of the novel peptide angiotensin-(1-12) by neonatal cardiac myocytes. PLoS ONE |
author_facet |
Sarfaraz Ahmad Jasmina Varagic Brian M Westwood Mark C Chappell Carlos M Ferrario |
author_sort |
Sarfaraz Ahmad |
title |
Uptake and metabolism of the novel peptide angiotensin-(1-12) by neonatal cardiac myocytes. |
title_short |
Uptake and metabolism of the novel peptide angiotensin-(1-12) by neonatal cardiac myocytes. |
title_full |
Uptake and metabolism of the novel peptide angiotensin-(1-12) by neonatal cardiac myocytes. |
title_fullStr |
Uptake and metabolism of the novel peptide angiotensin-(1-12) by neonatal cardiac myocytes. |
title_full_unstemmed |
Uptake and metabolism of the novel peptide angiotensin-(1-12) by neonatal cardiac myocytes. |
title_sort |
uptake and metabolism of the novel peptide angiotensin-(1-12) by neonatal cardiac myocytes. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2011-01-01 |
description |
Angiotensin-(1-12) [Ang-(1-12)] functions as an endogenous substrate for the productions of Ang II and Ang-(1-7) by a non-renin dependent mechanism. This study evaluated whether Ang-(1-12) is incorporated by neonatal cardiac myocytes and the enzymatic pathways of ¹²⁵I-Ang-(1-12) metabolism in the cardiac myocyte medium from WKY and SHR rats.The degradation of ¹²⁵I-Ang-(1-12) (1 nmol/L) in the cultured medium of these cardiac myocytes was evaluated in the presence and absence of inhibitors for angiotensin converting enzymes 1 and 2, neprilysin and chymase. In both strains uptake of ¹²⁵I-Ang-(1-12) by myocytes occurred in a time-dependent fashion. Uptake of intact Ang-(1-12) was significantly greater in cardiac myocytes of SHR as compared to WKY. In the absence of renin angiotensin system (RAS) enzymes inhibitors the hydrolysis of labeled Ang-(1-12) and the subsequent generation of smaller Ang peptides from Ang-(1-12) was significantly greater in SHR compared to WKY controls. ¹²⁵I-Ang-(1-12) degradation into smaller Ang peptides fragments was significantly inhibited (90% in WKY and 71% in SHR) in the presence of all RAS enzymes inhibitors. Further analysis of peptide fractions generated through the incubation of Ang-(1-12) in the myocyte medium demonstrated a predominant hydrolytic effect of angiotensin converting enzyme and neprilysin in WKY and an additional role for chymase in SHR.These studies demonstrate that neonatal myocytes sequester angiotensin-(1-12) and revealed the enzymes involved in the conversion of the dodecapeptide substrate to biologically active angiotensin peptides. |
url |
http://europepmc.org/articles/PMC3018413?pdf=render |
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