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A Comparative Peptidomic Characterization of Cultured Skeletal Muscle Tissues Derived From db/db Mice
As an important secretory organ, skeletal muscle has drawn attention as a potential target tissue for type 2 diabetic mellitus (T2DM). Recent peptidomics approaches have been applied to identify secreted peptides with potential bioactive. However, comprehensive analysis of the secreted peptides from...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828820/ https://www.ncbi.nlm.nih.gov/pubmed/31736878 http://dx.doi.org/10.3389/fendo.2019.00741 |
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author | Wu, Yanting Han, Mei Wang, Yan Gao, Yao Cui, Xianwei Xu, Pengfei Ji, Chenbo Zhong, Tianying You, Lianghui Zeng, Yu |
author_facet | Wu, Yanting Han, Mei Wang, Yan Gao, Yao Cui, Xianwei Xu, Pengfei Ji, Chenbo Zhong, Tianying You, Lianghui Zeng, Yu |
author_sort | Wu, Yanting |
collection | PubMed |
description | As an important secretory organ, skeletal muscle has drawn attention as a potential target tissue for type 2 diabetic mellitus (T2DM). Recent peptidomics approaches have been applied to identify secreted peptides with potential bioactive. However, comprehensive analysis of the secreted peptides from skeletal muscle tissues of db/db mice and elucidation of their possible roles in insulin resistance remains poorly characterized. Here, we adopted a label-free discovery using liquid chromatography tandem mass spectrometry (LC-MS/MS) technology and identified 63 peptides (42 up-regulated peptides and 21 down-regulated peptides) differentially secreted from cultured skeletal muscle tissues of db/db mice. Analysis of relative molecular mass (Mr), isoelectric point (pI) and distribution of Mr vs pI of differentially secreted peptides presented the general feature. Furthermore, Gene ontology (GO) and pathway analyses for the parent proteins made a comprehensive functional assessment of these differential peptides, indicating the enrichment in glycolysis/gluconeogenesis and striated muscle contraction processes. Intercellular location analysis pointed out most precursor proteins of peptides were cytoplasmic or cytoskeletal. Additionally, cleavage site analysis revealed that Lysine (N-terminal)-Alanine (C-terminal) and Lysine (N-terminal)-Leucine (C-terminal) represents the preferred cleavage sites for identified peptides and proceeding peptides respectively. Mapped to the precursors' sequences, most identified peptides were observed cleaved from creatine kinase m-type (KCRM) and fructose-bisphosphate aldolase A (Aldo A). Based on UniProt and Pfam database for specific domain structure or motif, 44 peptides out of total were positioned in the functional motif or domain from their parent proteins. Using C2C12 myotubes as cell model in vitro, we found several candidate peptides displayed promotive or inhibitory effects on insulin and mitochondrial-related pathways by an autocrine manner. Taken together, this study will encourage us to investigate the biologic functions and the potential regulatory mechanism of these secreted peptides from skeletal muscle tissues, thus representing a promising strategy to treat insulin resistance as well as the associated metabolic disorders. |
format | Online Article Text |
id | pubmed-6828820 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-68288202019-11-15 A Comparative Peptidomic Characterization of Cultured Skeletal Muscle Tissues Derived From db/db Mice Wu, Yanting Han, Mei Wang, Yan Gao, Yao Cui, Xianwei Xu, Pengfei Ji, Chenbo Zhong, Tianying You, Lianghui Zeng, Yu Front Endocrinol (Lausanne) Endocrinology As an important secretory organ, skeletal muscle has drawn attention as a potential target tissue for type 2 diabetic mellitus (T2DM). Recent peptidomics approaches have been applied to identify secreted peptides with potential bioactive. However, comprehensive analysis of the secreted peptides from skeletal muscle tissues of db/db mice and elucidation of their possible roles in insulin resistance remains poorly characterized. Here, we adopted a label-free discovery using liquid chromatography tandem mass spectrometry (LC-MS/MS) technology and identified 63 peptides (42 up-regulated peptides and 21 down-regulated peptides) differentially secreted from cultured skeletal muscle tissues of db/db mice. Analysis of relative molecular mass (Mr), isoelectric point (pI) and distribution of Mr vs pI of differentially secreted peptides presented the general feature. Furthermore, Gene ontology (GO) and pathway analyses for the parent proteins made a comprehensive functional assessment of these differential peptides, indicating the enrichment in glycolysis/gluconeogenesis and striated muscle contraction processes. Intercellular location analysis pointed out most precursor proteins of peptides were cytoplasmic or cytoskeletal. Additionally, cleavage site analysis revealed that Lysine (N-terminal)-Alanine (C-terminal) and Lysine (N-terminal)-Leucine (C-terminal) represents the preferred cleavage sites for identified peptides and proceeding peptides respectively. Mapped to the precursors' sequences, most identified peptides were observed cleaved from creatine kinase m-type (KCRM) and fructose-bisphosphate aldolase A (Aldo A). Based on UniProt and Pfam database for specific domain structure or motif, 44 peptides out of total were positioned in the functional motif or domain from their parent proteins. Using C2C12 myotubes as cell model in vitro, we found several candidate peptides displayed promotive or inhibitory effects on insulin and mitochondrial-related pathways by an autocrine manner. Taken together, this study will encourage us to investigate the biologic functions and the potential regulatory mechanism of these secreted peptides from skeletal muscle tissues, thus representing a promising strategy to treat insulin resistance as well as the associated metabolic disorders. Frontiers Media S.A. 2019-10-29 /pmc/articles/PMC6828820/ /pubmed/31736878 http://dx.doi.org/10.3389/fendo.2019.00741 Text en Copyright © 2019 Wu, Han, Wang, Gao, Cui, Xu, Ji, Zhong, You and Zeng. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Endocrinology Wu, Yanting Han, Mei Wang, Yan Gao, Yao Cui, Xianwei Xu, Pengfei Ji, Chenbo Zhong, Tianying You, Lianghui Zeng, Yu A Comparative Peptidomic Characterization of Cultured Skeletal Muscle Tissues Derived From db/db Mice |
title | A Comparative Peptidomic Characterization of Cultured Skeletal Muscle Tissues Derived From db/db Mice |
title_full | A Comparative Peptidomic Characterization of Cultured Skeletal Muscle Tissues Derived From db/db Mice |
title_fullStr | A Comparative Peptidomic Characterization of Cultured Skeletal Muscle Tissues Derived From db/db Mice |
title_full_unstemmed | A Comparative Peptidomic Characterization of Cultured Skeletal Muscle Tissues Derived From db/db Mice |
title_short | A Comparative Peptidomic Characterization of Cultured Skeletal Muscle Tissues Derived From db/db Mice |
title_sort | comparative peptidomic characterization of cultured skeletal muscle tissues derived from db/db mice |
topic | Endocrinology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6828820/ https://www.ncbi.nlm.nih.gov/pubmed/31736878 http://dx.doi.org/10.3389/fendo.2019.00741 |
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