Multiplexed temporal quantification of the exercise-regulated plasma peptidome
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Multiplexed temporal quantification of the exercise-regulated plasma peptidome. / Parker, Benjamin L; Burchfield, James G; Clayton, Daniel; Geddes, Thomas A; Payne, Richard J; Kiens, Bente; Wojtaszewski, Jørgen; Richter, Erik A.; James, David E.
I: Molecular and Cellular Proteomics, Bind 16, Nr. 12, 2017, s. 2055-2068.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Multiplexed temporal quantification of the exercise-regulated plasma peptidome
AU - Parker, Benjamin L
AU - Burchfield, James G
AU - Clayton, Daniel
AU - Geddes, Thomas A
AU - Payne, Richard J
AU - Kiens, Bente
AU - Wojtaszewski, Jørgen
AU - Richter, Erik A.
AU - James, David E
N1 - CURIS 2017 NEXS 341
PY - 2017
Y1 - 2017
N2 - Exercise is extremely beneficial to whole body health reducing the risk of a number of chronic human diseases. Some of these physiological benefits appear to be mediated via the secretion of peptide/protein hormones into the blood stream. The plasma peptidome contains the entire complement of low molecular weight endogenous peptides derived from secretion, protease activity and PTMs, and is a rich source of hormones. In the current study we have quantified the effects of intense exercise on the plasma peptidome to identify novel exercise regulated secretory factors in humans. We developed an optimised 2D-LC-MS/MS method and used multiple fragmentation methods including HCD and EThcD to analyse endogenous peptides. This resulted in quantification of 5,548 unique peptides during a time course of exercise and recovery. The plasma peptidome underwent dynamic and large changes during exercise on a time-scale of minutes with many rapidly reversible following exercise cessation. Among acutely regulated peptides, many were known hormones including insulin, glucagon, ghrelin, bradykinin, cholecystokinin and secretogranins validating the method. Prediction of bioactive peptides regulated with exercise identified C-terminal peptides from Transgelins, which were increased in plasma during exercise. In vitro experiments using synthetic peptides identified a role for transgelin peptides on the regulation of cell-cycle, extracellular matrix remodelling and cell migration. We investigated the effects of exercise on the regulation of PTMs and proteolytic processing by building a site-specific network of protease:substrate activity. Collectively, our deep peptidomic analysis of plasma revealed that exercise rapidly modulates the circulation of hundreds of bioactive peptides through a network of proteases and PTMs. These findings illustrate that peptidomics is an ideal method for quantifying changes in circulating factors on a global scale in response to physiological perturbations such as exercise. This will likely be a key method for pinpointing exercise regulated factors that generate health benefits.
AB - Exercise is extremely beneficial to whole body health reducing the risk of a number of chronic human diseases. Some of these physiological benefits appear to be mediated via the secretion of peptide/protein hormones into the blood stream. The plasma peptidome contains the entire complement of low molecular weight endogenous peptides derived from secretion, protease activity and PTMs, and is a rich source of hormones. In the current study we have quantified the effects of intense exercise on the plasma peptidome to identify novel exercise regulated secretory factors in humans. We developed an optimised 2D-LC-MS/MS method and used multiple fragmentation methods including HCD and EThcD to analyse endogenous peptides. This resulted in quantification of 5,548 unique peptides during a time course of exercise and recovery. The plasma peptidome underwent dynamic and large changes during exercise on a time-scale of minutes with many rapidly reversible following exercise cessation. Among acutely regulated peptides, many were known hormones including insulin, glucagon, ghrelin, bradykinin, cholecystokinin and secretogranins validating the method. Prediction of bioactive peptides regulated with exercise identified C-terminal peptides from Transgelins, which were increased in plasma during exercise. In vitro experiments using synthetic peptides identified a role for transgelin peptides on the regulation of cell-cycle, extracellular matrix remodelling and cell migration. We investigated the effects of exercise on the regulation of PTMs and proteolytic processing by building a site-specific network of protease:substrate activity. Collectively, our deep peptidomic analysis of plasma revealed that exercise rapidly modulates the circulation of hundreds of bioactive peptides through a network of proteases and PTMs. These findings illustrate that peptidomics is an ideal method for quantifying changes in circulating factors on a global scale in response to physiological perturbations such as exercise. This will likely be a key method for pinpointing exercise regulated factors that generate health benefits.
KW - Exercise
KW - Peptide hormone
KW - EThcD
KW - Mass spectrometry
KW - Peptidomics
KW - Physiology
KW - Plasma or serum analysis
KW - Proteases
U2 - 10.1074/mcp.RA117.000020
DO - 10.1074/mcp.RA117.000020
M3 - Journal article
C2 - 28982716
VL - 16
SP - 2055
EP - 2068
JO - Molecular and Cellular Proteomics
JF - Molecular and Cellular Proteomics
SN - 1535-9476
IS - 12
ER -
ID: 184391740