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. 2021 Sep 1:8:723858.
doi: 10.3389/fmolb.2021.723858. eCollection 2021.

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

Afnan Saleh Al-Menhali  1   2 , Cali Anderson  3 , Alexander V Gourine  4 , Andrey Y Abramov  5 , Alicia D'Souza  3 , Morana Jaganjac  1   6
Affiliations

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

Afnan Saleh Al-Menhali et al. Front Mol Biosci. .

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.

Keywords: 4-hydroxynonenal; exercise; left ventricle; oxidative stress; proteomics.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
(A) PLS scatter plot showing the difference between control and exercised mice. (B) Heat map of semiquantitative assessment of ventricular proteins upregulated/downregulated with exercise. (C) Volcano plot of differentially expressed left ventricular tissue proteins between the control and exercised groups. The significantly upregulated and downregulated proteins are indicated with red dots, while those with p < 0.01 are indicated with dark red dots. (D–F) Repartition of upregulated proteins identified in the left ventricle of the heart tissues of exercised mice by (D) protein classes, (E) molecular functions, and (F) biological processes using the bioinformatics algorithms of the PANTHER classification system (version 15.0). (G) Biological pathways regulated by proteins altered by exercise. Proteins upregulated in ≥6 samples were analyzed using the Reactome database for Mus musculus, and only those with Entities FDR <0.1 are shown. bp value: represents the probability that the overlap between the query has occurred by1 chance.
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