Abstract
Exercise has been shown to improve health status and prevent chronic diseases. In contrast, overtraining can lead to maladaptation and detrimental health outcomes. These outcomes appear to be mediated in part by released peptides and, potentially, alterations in protein abundances and their modified forms, termed proteoforms. Proteoform biomarkers that either predict the beneficial effects of exercise or indicate (mal)adaptation are yet to be elucidated. Thus, we assessed the influence of high-intensity interval exercise (HIIE) on the human serum proteome to identify novel exercise-regulated proteoforms. To this end, a top-down proteomics approach was used, whereby two-dimensional gel electrophoresis was used to resolve and differentially profile intact proteoforms, followed by protein identification via liquid chromatography-tandem mass spectrometry. Blood was collected from six young-adult healthy males, pre-exercise and 5 min and 1 h post-exercise. Exercise consisted of a maximal cycle ergometer test followed by 8 min × 1 min high-intensity intervals at 90% Wmax, with 1 min non-active recovery between intervals. Twenty resolved serum proteoforms changed significantly in abundance at 5 min and/or 1 h post-HIIE, including apolipoproteins, serpins (protease inhibitors), and immune system proteins, known to have broad anti-inflammatory and antioxidant effects, involvement in lipid clearance, and cardio-/neuro-protective effects. This initial screening for potential biomarkers indicates that a top-down analytical proteomic approach may prove useful in further characterizing the response to exercise and in understanding the molecular mechanisms that lead to health benefits, as well as identifying novel biomarkers for exercise (mal)adaptation.
Highlights
It is well-documented that regular exercise is associated with numerous health benefits (Smorawinski et al, 2000; Warburton et al, 2006)
During highintensity interval exercise (HIIE) trials, mean heart rates were >90% of the participants predicted HRmax (94.1 ± 5.3%) and immediately following they all responded ≥19/20 on the Borg scale (Borg, 1998). This confirmed that the HIIE trial was high-intensity and successful in exhausting the participants
2DE coupled with LC-MS/MS enabled the resolution and identification of differentially abundant intact proteoforms, unlikely to have been detected by a bottom-up MS-based ‘shotgun’ proteomic approach nor through targeted proteomic assays since both methodologies generally assess only gross changes in abundances, with critical information pertaining to intact proteoforms and their unique physicochemical characteristics lost or unaccounted for. This is the first study to sequentially assess the human serum proteome following HIIE using a comprehensive topdown approach to identify significant changes in proteoforms (Jungblut et al, 2008; Thiede et al, 2013; Coorssen and Yergey, 2015; Zhan et al, 2018), implicating proteoforms associated with immune function, coagulation cascades, vitamins, protein and lipid metabolism, and proliferative and apoptotic pathways. Many of these novel exercise-regulated proteoforms have been previously suggested as potential therapeutic targets in chronic diseases [i.e., Alzheimer’s disease (AD), type II diabetes mellitus and cardiovascular disease (CVD)] (Booth et al, 2012), supporting the notion that these proteoforms may mediate the longer-term health benefits associated with exercise training
Summary
It is well-documented that regular exercise is associated with numerous health benefits (Smorawinski et al, 2000; Warburton et al, 2006). Mechanisms that lead to the numerous health benefits associated with exercise training may be stimulated through multiple bouts of acute (single-session) exercise, i.e., high-intensity interval exercise (HIIE), that occurs over a time-period of training (Hojman et al, 2018). A cross-sectional assessment of the effects of high and low levels of physical activity on the plasma proteome utilizing an aptamer-based SOMAscan proteomic assay has been reported (Santos-Parker et al, 2018). These have found large perturbations in bioactive peptides, metabolic pathways (e.g., glycolysis), cell cycle regulatory proteins, and proteins related to immunity. Untargeted and comprehensive assessments of plasma and/or serum proteomes in response to HIIE – inclusive of gene, splice, and post-translationally modified variants (i.e., proteoforms), which are influenced by metabolic needs and health/disease state (Jungblut et al, 2008; Thiede et al, 2013; Coorssen and Yergey, 2015) – are yet to be carried out
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
