Suprabasin-derived bioactive peptides identified by plasma peptidomics

Abstract Identification of low-abundance, low-molecular-weight native peptides using non-tryptic plasma has long remained an unmet challenge, leaving potential bioactive/biomarker peptides undiscovered. We have succeeded in efficiently removing high-abundance plasma proteins to enrich and comprehens...

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Main Authors: Tomomi Taguchi, Yoshio Kodera, Kazuhito Oba, Tatsuya Saito, Yuzuru Nakagawa, Yusuke Kawashima, Masayoshi Shichiri
Format: Article
Language:English
Published: Nature Portfolio 2021-01-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-020-79353-4
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author Tomomi Taguchi
Yoshio Kodera
Kazuhito Oba
Tatsuya Saito
Yuzuru Nakagawa
Yusuke Kawashima
Masayoshi Shichiri
author_facet Tomomi Taguchi
Yoshio Kodera
Kazuhito Oba
Tatsuya Saito
Yuzuru Nakagawa
Yusuke Kawashima
Masayoshi Shichiri
author_sort Tomomi Taguchi
collection DOAJ
description Abstract Identification of low-abundance, low-molecular-weight native peptides using non-tryptic plasma has long remained an unmet challenge, leaving potential bioactive/biomarker peptides undiscovered. We have succeeded in efficiently removing high-abundance plasma proteins to enrich and comprehensively identify low-molecular-weight native peptides using mass spectrometry. Native peptide sequences were chemically synthesized and subsequent functional analyses resulted in the discovery of three novel bioactive polypeptides derived from an epidermal differentiation marker protein, suprabasin. SBSN_HUMAN[279–295] potently suppressed food/water intake and induced locomotor activity when injected intraperitoneally, while SBSN_HUMAN[225–237] and SBSN_HUMAN[243–259] stimulated the expression of proinflammatory cytokines via activation of NF-κB signaling in vascular cells. SBSN_HUMAN[225–237] and SBSN_HUMAN[279–295] immunoreactivities were present in almost all human organs analyzed, while immunoreactive SBSN_HUMAN[243–259] was abundant in the liver and pancreas. Human macrophages expressed the three suprabasin-derived peptides. This study illustrates a new approach for discovering unknown bioactive peptides in plasma via the generation of peptide libraries using a novel peptidomic strategy.
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spelling doaj.art-cdc5cf7e975746e1bf9c6d7737b912812022-12-21T21:27:59ZengNature PortfolioScientific Reports2045-23222021-01-0111111710.1038/s41598-020-79353-4Suprabasin-derived bioactive peptides identified by plasma peptidomicsTomomi Taguchi0Yoshio Kodera1Kazuhito Oba2Tatsuya Saito3Yuzuru Nakagawa4Yusuke Kawashima5Masayoshi Shichiri6Department of Endocrinology, Diabetes and Metabolism, Kitasato University School of MedicineDepartment of Physics, Kitasato University School of ScienceDepartment of Endocrinology, Diabetes and Metabolism, Kitasato University School of MedicineDepartment of Endocrinology, Diabetes and Metabolism, Kitasato University School of MedicineDepartment of Physics, Kitasato University School of ScienceDepartment of Physics, Kitasato University School of ScienceDepartment of Endocrinology, Diabetes and Metabolism, Kitasato University School of MedicineAbstract Identification of low-abundance, low-molecular-weight native peptides using non-tryptic plasma has long remained an unmet challenge, leaving potential bioactive/biomarker peptides undiscovered. We have succeeded in efficiently removing high-abundance plasma proteins to enrich and comprehensively identify low-molecular-weight native peptides using mass spectrometry. Native peptide sequences were chemically synthesized and subsequent functional analyses resulted in the discovery of three novel bioactive polypeptides derived from an epidermal differentiation marker protein, suprabasin. SBSN_HUMAN[279–295] potently suppressed food/water intake and induced locomotor activity when injected intraperitoneally, while SBSN_HUMAN[225–237] and SBSN_HUMAN[243–259] stimulated the expression of proinflammatory cytokines via activation of NF-κB signaling in vascular cells. SBSN_HUMAN[225–237] and SBSN_HUMAN[279–295] immunoreactivities were present in almost all human organs analyzed, while immunoreactive SBSN_HUMAN[243–259] was abundant in the liver and pancreas. Human macrophages expressed the three suprabasin-derived peptides. This study illustrates a new approach for discovering unknown bioactive peptides in plasma via the generation of peptide libraries using a novel peptidomic strategy.https://doi.org/10.1038/s41598-020-79353-4
spellingShingle Tomomi Taguchi
Yoshio Kodera
Kazuhito Oba
Tatsuya Saito
Yuzuru Nakagawa
Yusuke Kawashima
Masayoshi Shichiri
Suprabasin-derived bioactive peptides identified by plasma peptidomics
Scientific Reports
title Suprabasin-derived bioactive peptides identified by plasma peptidomics
title_full Suprabasin-derived bioactive peptides identified by plasma peptidomics
title_fullStr Suprabasin-derived bioactive peptides identified by plasma peptidomics
title_full_unstemmed Suprabasin-derived bioactive peptides identified by plasma peptidomics
title_short Suprabasin-derived bioactive peptides identified by plasma peptidomics
title_sort suprabasin derived bioactive peptides identified by plasma peptidomics
url https://doi.org/10.1038/s41598-020-79353-4
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