Proteomic Analysis of Cardiac Adaptation to Exercise by High Resolution Mass Spectrometry.

Morana Jaganjac,Cali Anderson,Alicia D’Souza,Alexander V. Gourine,Andrey Y. Abramov,Afnan Saleh Al-Menhali

doi:10.3389/fmolb.2021.723858

Abstract

Regular exercise has many health benefits, among which is a significant reduction of cardiovascular risk. Although many beneficial effects of exercise are well described, the exact mechanisms by which exercise confers cardiovascular benefits are yet to be fully understood. In the current study, we have used high resolution mass spectrometry to determine the proteomic responses of the heart to exercise training in mice. The impact of exercise-induced oxidative stress on modifications of cardiomyocyte proteins with lipid peroxidation biomarker 4-hydroxynonenal (4-HNE) was examined as well. Fourteen male mice were randomized into the control (sedentary) group and the exercise group that was subjected to a swim exercise training program for 5 days a week for 5 months. Proteins were isolated from the left ventricular tissue, fractionated and digested for shotgun proteomics. Peptides were separated by nanoliquid chromatography and analyzed on an Orbitrap Fusion mass spectrometer using high-energy collision–induced dissociation and electron transfer dissociation fragmentation. We identified distinct ventricular protein signatures established in response to exercise training. Comparative proteomics identified 23 proteins that were upregulated and 37 proteins that were downregulated with exercise, in addition to 65 proteins that were identified only in ventricular tissue samples of exercised mice. Most of the proteins specific to exercised mice are involved in respiratory electron transport and/or implicated in glutathione conjugation. Additionally, 10 proteins were found to be modified with 4-HNE. This study provides new data on the effects of exercise on the cardiac proteome and contributes to our understanding of the molecular mechanisms underlying the beneficial effects of exercise on the heart.

Highlights

In the early 1950s, Morris and others showed the association between physical activity and reduced deaths from coronary heart disease, which led to increased scientific interest in the potential of physical activity to combat diseases (Morris et al, 1953)
Further analyses were based on the criteria that the protein/peptide must be common for ≥6 tissue samples of the same group of animals
A total of 804 proteins were identified in the control group with a total number of 2,913 peptides, while 816 proteins were found in the exercised group with a total of 3,254 peptides

Summary

Introduction

In the early 1950s, Morris and others showed the association between physical activity and reduced deaths from coronary heart disease, which led to increased scientific interest in the potential of physical activity to combat diseases (Morris et al, 1953). Current knowledge shows a clear link between an active lifestyle and overall health. Physical exercise is found to benefit the heart as it increases aerobic fitness (VO2max), enhances contraction, and accelerates relaxation, as well as Exercise-Induced Changes of Heart Proteome decreasing the risk of developing cardiomyopathies (Roof et al, 2013). Endurance exercise can trigger several adaptational mechanisms resulting in exercise-induced cardioprotection changes. Those changes include an enhanced antioxidant defense system with increased expression of glutathione peroxidase-1 and manganese superoxide dismutase. Cardiac function is improved due to changes in the expression of enzymes involved in energy metabolism (Burniston and Hoffman, 2011)

Objectives

Results

Discussion

Conclusion