Brand new study reveals a most likely proteome signature for reductive stress cardiomyopathy

reductive stress cardiomyopathy

reductive stress cardiomyopathy

Two years ago, University of Alabama at Birmingham associates and researchers reported that reductive stress -; an imbalance in the normal oxidation/reduction, or redox, homeostasis -; caused pathological modifications associated with cardiac arrest in a mouse model. This was a follow-up to their 2018 scientific research study that found about one in six cardiac arrest clients reveals reductive tension.

Now they have actually extended their description of modifications triggered by reductive tension to explain modifications in the proteome of heart cells in mice, disclosing a likely proteome signature for reductive tension cardiomyopathy. A proteome is the complement of proteins expressed in a cell or tissue.

Using tandem mass spectrometry, researchers led by Rajasekaran Namakkal-Soorappan, Ph.D., associate professor in the UAB Department of Pathology, Division of Cellular and molecular Pathology, looked at differential protein expression in between control hearts and reductive-stress hearts in a mouse model of persistent reductive stress.

They discovered about 560 proteins were differentially revealed, and 32 proteins were substantially altered -; 20 being upregulated and 12 downregulated. The reductive tension mouse model is brought on by a constitutively active NRF2, the redox sensing unit that preserves redox homeostasis in cells.

Through gene ontology and path analysis, the scientists found that most of the differentially expressed proteins are associated with stress-related pathways such as antioxidants, NADPH, protein quality control and others. Proteins associated with mitochondrial respiration, lipophagy and cardiac rhythm were considerably decreased in the reductive tension hearts.

The most significantly changed subset of proteins remained in the glutathione household. Glutathione is an antioxidant, active in redox homeostasis, that can exist in a minimized or oxidized form.

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Remarkably, the levels of about half of 104 transformed proteins were found not to associate with levels of their messenger RNAs, the gene message that reads by ribosomes to make a protein. The reason for this asynchrony is not understood.

In association with the transformed proteome, the reductive tension mice showed pathological cardiac improvement. This cardiomyopathy makes it harder for the heart to pump blood, and it can lead to cardiac arrest. The scientists likewise discovered post-translational adjustments such as oxidation, N-ethylmaleimide, methionine loss and acetylation in the reductive tension hearts.


Under reductive stress, we observed downregulation of several myocardial adaptation or rescue pathways and upregulation of pathophysiological processes, which are associated with reductive stress cardiomyopathy over time. Thus, our results provide a rationale to develop personalized antioxidant therapeutic strategies to avoid reductive stress-mediated proteome alterations in humans.”

Rajasekaran Namakkal-Soorappan, Ph.D., associate professor in the UAB Department of Pathology, Division of Molecular and Cellular Pathology