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Proteomic signatures of acute oxidative stress response to paraquat in the mouse heart

Vishantie Dostal, Silas D. Wood, Cody T. Thomas, Yu Han, View ORCID ProfileEdward Lau, View ORCID ProfileMaggie P.Y. Lam
doi: https://doi.org/10.1101/2020.05.29.124487
Vishantie Dostal
1Departments of Medicine/Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
2Biochemistry & Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
3Consortium for Fibrosis Research & Translation, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
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Silas D. Wood
1Departments of Medicine/Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
2Biochemistry & Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
3Consortium for Fibrosis Research & Translation, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
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Cody T. Thomas
1Departments of Medicine/Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
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Yu Han
1Departments of Medicine/Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
2Biochemistry & Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
3Consortium for Fibrosis Research & Translation, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
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Edward Lau
1Departments of Medicine/Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
3Consortium for Fibrosis Research & Translation, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
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  • ORCID record for Edward Lau
Maggie P.Y. Lam
1Departments of Medicine/Cardiology, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
2Biochemistry & Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
3Consortium for Fibrosis Research & Translation, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA
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  • ORCID record for Maggie P.Y. Lam
  • For correspondence: maggie.lam@cuanschutz.edu
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Abstract

The heart is sensitive to oxidative damage but a global view on how the cardiac proteome responds to oxidative stressors has yet to fully emerge. Using quantitative tandem mass spectrometry, we assessed the effects of acute exposure of the oxidative stress inducer paraquat on protein expression in mouse hearts. We observed widespread protein expression changes in the paraquat-exposed heart especially in organelle-containing subcellular fractions. During cardiac response to acute oxidative stress, proteome changes are consistent with a rapid reduction of mitochondrial metabolism, coupled with activation of multiple antioxidant proteins, reduction of protein synthesis and remediation of proteostasis. In addition to differential expression, we saw evidence of spatial reorganizations of the cardiac proteome including the translocation of hexokinase 2 to more soluble fractions. Treatment with the antioxidants Tempol and MitoTEMPO reversed many proteomic signatures of paraquat but this reversal was incomplete. We also identified a number of proteins with unknown function in the heart to be triggered by paraquat, suggesting they may have functions in oxidative stress response. Surprisingly, protein expression changes in the heart correlate poorly with those in the lung, consistent with differential sensitivity or stress response in these two organs. The results provide insights into oxidative stress responses in the heart and may avail the search for new therapeutic targets.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted May 31, 2020.
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Proteomic signatures of acute oxidative stress response to paraquat in the mouse heart
Vishantie Dostal, Silas D. Wood, Cody T. Thomas, Yu Han, Edward Lau, Maggie P.Y. Lam
bioRxiv 2020.05.29.124487; doi: https://doi.org/10.1101/2020.05.29.124487
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Proteomic signatures of acute oxidative stress response to paraquat in the mouse heart
Vishantie Dostal, Silas D. Wood, Cody T. Thomas, Yu Han, Edward Lau, Maggie P.Y. Lam
bioRxiv 2020.05.29.124487; doi: https://doi.org/10.1101/2020.05.29.124487

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