Characterisation of preproendothelin-1 derived peptides identifies Endothelin-Like Domain Peptide as a modulator of Endothelin-1

Abstract Endothelin-1 (ET-1) is involved in the pathogenesis of cardiac and renal diseases, and in the progression of tumour growth in cancer, but current diagnosis and treatment remain inadequate. Peptides derived from the 212 amino acid precursor preproendothelin-1 (ppET-1) may have utility as bio...

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Autores principales:	Jale Yuzugulen, Julie A. Douthwaite, Elizabeth G. Wood, Inmaculada C. Villar, Nimesh S. A. Patel, James Jegard, Hubert Gaertner, Irène Rossitto-Borlat, Keith Rose, Oliver Hartley, Pedro R. Cutillas, Amrita Ahluwalia, Roger Corder
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c88405d4ef9a4272ab9b01473d274a6f
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spelling	oai:doaj.org-article:c88405d4ef9a4272ab9b01473d274a6f2021-12-02T15:18:52ZCharacterisation of preproendothelin-1 derived peptides identifies Endothelin-Like Domain Peptide as a modulator of Endothelin-110.1038/s41598-017-05365-22045-2322https://doaj.org/article/c88405d4ef9a4272ab9b01473d274a6f2017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05365-2https://doaj.org/toc/2045-2322Abstract Endothelin-1 (ET-1) is involved in the pathogenesis of cardiac and renal diseases, and in the progression of tumour growth in cancer, but current diagnosis and treatment remain inadequate. Peptides derived from the 212 amino acid precursor preproendothelin-1 (ppET-1) may have utility as biomarkers, or cause biological effects that are unaffected by endothelin receptor antagonists. Here, we used specific immunoassays and LC-MS/MS to identify NT-proET-1 (ppET-1[18–50]), Endothelin-Like Domain Peptide (ELDP, ppET-1[93–166]) and CT-proET-1 (ppET-1[169–212]) in conditioned media from cultured endothelial cells. Synthesis of these peptides correlated with ET-1, and plasma ELDP and CT-proET-1 were elevated in patients with chronic heart failure. Clearance rates of NT-proET-1, ELDP and CT-proET-1 were determined after i.v. injection in anaesthetised rats. CT-proET-1 had the slowest systemic clearance, hence providing a biological basis for it being a better biomarker of ET-1 synthesis. ELDP contains the evolutionary conserved endothelin-like domain sequence, which potentially confers biological activity. On isolated arteries ELDP lacked direct vasoconstrictor effects. However, it enhanced ET-1 vasoconstriction and prolonged the increase in blood pressure in anaesthetised rats. ELDP may therefore contribute to disease pathogenesis by augmenting ET-1 responses.Jale YuzugulenJulie A. DouthwaiteElizabeth G. WoodInmaculada C. VillarNimesh S. A. PatelJames JegardHubert GaertnerIrène Rossitto-BorlatKeith RoseOliver HartleyPedro R. CutillasAmrita AhluwaliaRoger CorderNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-15 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jale Yuzugulen Julie A. Douthwaite Elizabeth G. Wood Inmaculada C. Villar Nimesh S. A. Patel James Jegard Hubert Gaertner Irène Rossitto-Borlat Keith Rose Oliver Hartley Pedro R. Cutillas Amrita Ahluwalia Roger Corder Characterisation of preproendothelin-1 derived peptides identifies Endothelin-Like Domain Peptide as a modulator of Endothelin-1
description	Abstract Endothelin-1 (ET-1) is involved in the pathogenesis of cardiac and renal diseases, and in the progression of tumour growth in cancer, but current diagnosis and treatment remain inadequate. Peptides derived from the 212 amino acid precursor preproendothelin-1 (ppET-1) may have utility as biomarkers, or cause biological effects that are unaffected by endothelin receptor antagonists. Here, we used specific immunoassays and LC-MS/MS to identify NT-proET-1 (ppET-1[18–50]), Endothelin-Like Domain Peptide (ELDP, ppET-1[93–166]) and CT-proET-1 (ppET-1[169–212]) in conditioned media from cultured endothelial cells. Synthesis of these peptides correlated with ET-1, and plasma ELDP and CT-proET-1 were elevated in patients with chronic heart failure. Clearance rates of NT-proET-1, ELDP and CT-proET-1 were determined after i.v. injection in anaesthetised rats. CT-proET-1 had the slowest systemic clearance, hence providing a biological basis for it being a better biomarker of ET-1 synthesis. ELDP contains the evolutionary conserved endothelin-like domain sequence, which potentially confers biological activity. On isolated arteries ELDP lacked direct vasoconstrictor effects. However, it enhanced ET-1 vasoconstriction and prolonged the increase in blood pressure in anaesthetised rats. ELDP may therefore contribute to disease pathogenesis by augmenting ET-1 responses.
format	article
author	Jale Yuzugulen Julie A. Douthwaite Elizabeth G. Wood Inmaculada C. Villar Nimesh S. A. Patel James Jegard Hubert Gaertner Irène Rossitto-Borlat Keith Rose Oliver Hartley Pedro R. Cutillas Amrita Ahluwalia Roger Corder
author_facet	Jale Yuzugulen Julie A. Douthwaite Elizabeth G. Wood Inmaculada C. Villar Nimesh S. A. Patel James Jegard Hubert Gaertner Irène Rossitto-Borlat Keith Rose Oliver Hartley Pedro R. Cutillas Amrita Ahluwalia Roger Corder
author_sort	Jale Yuzugulen
title	Characterisation of preproendothelin-1 derived peptides identifies Endothelin-Like Domain Peptide as a modulator of Endothelin-1
title_short	Characterisation of preproendothelin-1 derived peptides identifies Endothelin-Like Domain Peptide as a modulator of Endothelin-1
title_full	Characterisation of preproendothelin-1 derived peptides identifies Endothelin-Like Domain Peptide as a modulator of Endothelin-1
title_fullStr	Characterisation of preproendothelin-1 derived peptides identifies Endothelin-Like Domain Peptide as a modulator of Endothelin-1
title_full_unstemmed	Characterisation of preproendothelin-1 derived peptides identifies Endothelin-Like Domain Peptide as a modulator of Endothelin-1
title_sort	characterisation of preproendothelin-1 derived peptides identifies endothelin-like domain peptide as a modulator of endothelin-1
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c88405d4ef9a4272ab9b01473d274a6f
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Characterisation of preproendothelin-1 derived peptides identifies Endothelin-Like Domain Peptide as a modulator of Endothelin-1

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