GIP_HUMAN[22–51] is a new proatherogenic peptide identified by native plasma peptidomics

Abstract We recently established a new plasma peptidomic technique and comprehensively identified a large number of low-molecular weight and low-abundance native peptides using a single drop of human plasma. To discover a novel polypeptide that potently modulates the cardiovascular system, we perfor...

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Autores principales:	Tsuguto Masaki, Yoshio Kodera, Michishige Terasaki, Kazumi Fujimoto, Tsutomu Hirano, Masayoshi Shichiri
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/82b71081798b42109aeddb00f459df30
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spelling	oai:doaj.org-article:82b71081798b42109aeddb00f459df302021-12-02T16:14:03ZGIP_HUMAN[22–51] is a new proatherogenic peptide identified by native plasma peptidomics10.1038/s41598-021-93862-w2045-2322https://doaj.org/article/82b71081798b42109aeddb00f459df302021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-93862-whttps://doaj.org/toc/2045-2322Abstract We recently established a new plasma peptidomic technique and comprehensively identified a large number of low-molecular weight and low-abundance native peptides using a single drop of human plasma. To discover a novel polypeptide that potently modulates the cardiovascular system, we performed a bioinformatics analysis of the large-scale identification results, sequentially synthesized the selected peptide sequences, tested their biological activities, and identified a 30-amino-acid proatherogenic peptide, GIP_HUMAN[22–51], as a potent proatherosclerotic peptide hormone. GIP_HUMAN[22–51] has a common precursor with the glucose-dependent insulinotropic polypeptide (GIP) and is located immediately N-terminal to GIP. Chronic infusion of GIP_HUMAN[22–51] into ApoE −/− mice accelerated the development of aortic atherosclerotic lesions, which were inhibited by co-infusions with an anti-GIP_HUMAN[22–51] antibody. GIP_HUMAN[22–51] increased the serum concentrations of many inflammatory and proatherogenic proteins, whereas neutralising antibodies reduced their levels. GIP_HUMAN[22–51] induced IκB-α degradation and nuclear translocation of NF-κB in human vascular endothelial cells and macrophages. Immunoreactive GIP_HUMAN[22–51] was detected in human tissues but there was no colocalization with the GIP. The plasma GIP_HUMAN[22–51] concentration in healthy humans determined using a stable-isotope tagged peptide was approximately 0.6 nM. This study discovered a novel endogenous proatherogenic peptide by using a human plasma native peptidomic resource.Tsuguto MasakiYoshio KoderaMichishige TerasakiKazumi FujimotoTsutomu HiranoMasayoshi ShichiriNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tsuguto Masaki Yoshio Kodera Michishige Terasaki Kazumi Fujimoto Tsutomu Hirano Masayoshi Shichiri GIP_HUMAN[22–51] is a new proatherogenic peptide identified by native plasma peptidomics
description	Abstract We recently established a new plasma peptidomic technique and comprehensively identified a large number of low-molecular weight and low-abundance native peptides using a single drop of human plasma. To discover a novel polypeptide that potently modulates the cardiovascular system, we performed a bioinformatics analysis of the large-scale identification results, sequentially synthesized the selected peptide sequences, tested their biological activities, and identified a 30-amino-acid proatherogenic peptide, GIP_HUMAN[22–51], as a potent proatherosclerotic peptide hormone. GIP_HUMAN[22–51] has a common precursor with the glucose-dependent insulinotropic polypeptide (GIP) and is located immediately N-terminal to GIP. Chronic infusion of GIP_HUMAN[22–51] into ApoE −/− mice accelerated the development of aortic atherosclerotic lesions, which were inhibited by co-infusions with an anti-GIP_HUMAN[22–51] antibody. GIP_HUMAN[22–51] increased the serum concentrations of many inflammatory and proatherogenic proteins, whereas neutralising antibodies reduced their levels. GIP_HUMAN[22–51] induced IκB-α degradation and nuclear translocation of NF-κB in human vascular endothelial cells and macrophages. Immunoreactive GIP_HUMAN[22–51] was detected in human tissues but there was no colocalization with the GIP. The plasma GIP_HUMAN[22–51] concentration in healthy humans determined using a stable-isotope tagged peptide was approximately 0.6 nM. This study discovered a novel endogenous proatherogenic peptide by using a human plasma native peptidomic resource.
format	article
author	Tsuguto Masaki Yoshio Kodera Michishige Terasaki Kazumi Fujimoto Tsutomu Hirano Masayoshi Shichiri
author_facet	Tsuguto Masaki Yoshio Kodera Michishige Terasaki Kazumi Fujimoto Tsutomu Hirano Masayoshi Shichiri
author_sort	Tsuguto Masaki
title	GIP_HUMAN[22–51] is a new proatherogenic peptide identified by native plasma peptidomics
title_short	GIP_HUMAN[22–51] is a new proatherogenic peptide identified by native plasma peptidomics
title_full	GIP_HUMAN[22–51] is a new proatherogenic peptide identified by native plasma peptidomics
title_fullStr	GIP_HUMAN[22–51] is a new proatherogenic peptide identified by native plasma peptidomics
title_full_unstemmed	GIP_HUMAN[22–51] is a new proatherogenic peptide identified by native plasma peptidomics
title_sort	gip_human[22–51] is a new proatherogenic peptide identified by native plasma peptidomics
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/82b71081798b42109aeddb00f459df30
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GIP_HUMAN[22–51] is a new proatherogenic peptide identified by native plasma peptidomics

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