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Home / Equine Research Bank / Genes (Basel) / Enriched Pathways of Calcium Regulation, Cellular/Oxidative ...
Genes2022; 13(10); doi: 10.3390/genes13101853

Enriched Pathways of Calcium Regulation, Cellular/Oxidative Stress, Inflammation, and Cell Proliferation Characterize Gluteal Muscle of Standardbred Horses between Episodes of Recurrent Exertional Rhabdomyolysis.

Abstract: Certain Standardbred racehorses develop recurrent exertional rhabdomyolysis (RER-STD) for unknown reasons. We compared gluteal muscle histopathology and gene/protein expression between Standardbreds with a history of, but not currently experiencing rhabdomyolysis (N = 9), and race-trained controls (N = 7). Eight RER-STD had a few mature fibers with small internalized myonuclei, one out of nine had histologic evidence of regeneration and zero out of nine degeneration. However, RER-STD versus controls had 791/13,531 differentially expressed genes (DEG). The top three gene ontology (GO) enriched pathways for upregulated DEG (N = 433) were inflammation/immune response (62 GO terms), cell proliferation (31 GO terms), and hypoxia/oxidative stress (31 GO terms). Calcium ion regulation (39 GO terms), purine nucleotide metabolism (32 GO terms), and electron transport (29 GO terms) were the top three enriched GO pathways for down-regulated DEG (N = 305). DEG regulated RYR1 and sarcoplasmic reticulum calcium stores. Differentially expressed proteins (DEP ↑N = 50, ↓N = 12) involved the sarcomere (24% of DEP), electron transport (23%), metabolism (20%), inflammation (6%), cell/oxidative stress (7%), and other (17%). DEP included ↑superoxide dismutase, ↑catalase, and DEP/DEG included several cysteine-based antioxidants. In conclusion, gluteal muscle of RER-susceptible Standardbreds is characterized by perturbation of pathways for calcium regulation, cellular/oxidative stress, inflammation, and cellular regeneration weeks after an episode of rhabdomyolysis that could represent therapeutic targets.
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Publication Date: 2022-10-14 PubMed ID: 36292738PubMed Central: PMC9601720DOI: 10.3390/genes13101853Google Scholar: Lookup
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  • Journal Article
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  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigates the characteristics of the gluteal muscles in Standardbred racehorses suffering from recurrent exertional rhabdomyolysis (RER-STD), focusing on the associated changes in calcium regulation, cellular stress response, inflammation, and cell proliferation pathways. Anomalies in these pathways could help develop therapies for this condition.

Objective of the Research

  • The research aims to shed light on the unknown causes of recurrent exertional rhabdomyolysis (RER-STD) in certain Standardbred racehorses by studying the changes in the gluteal muscle history and gene/protein expression.

Research Methodology

  • Gluteal muscle tissue samples were collected from RER-STD Standardbred horses that were not currently having an episode. These samples were compared with those taken from healthy, race-trained Standardbred horses (the control group).

Research Findings

  • Muscle histopathology showed a small number of mature fibers with internalized myonuclei in the RER-STD group. Still, there was no clear evidence of muscle tissue degeneration or regeneration.
  • Gene expression analysis showed differences in 791 out of 13,531 genes between the RER-STD and control groups.
  • Upregulated genes (those with increased expression) in the RER-STD group were primarily associated with inflammation, immune response, cell proliferation, and hypoxia/oxidative stress.
  • Downregulated genes (those with decreased expression) were mostly involved in calcium ion regulation, purine nucleotide metabolism, and electron transport.
  • Changes in protein expression (both increase and decrease) affected the sarcomere, electron transport, metabolism, inflammation, and cellular stress response.
  • The research also recorded changes in the expression of specific proteins and genes like superoxide dismutase, catalase, and several cysteine-based antioxidants.

Conclusion

  • The study concludes that the gluteal muscle in Standardbred horses susceptible to RER-STD exhibits disturbances in pathways relating to calcium regulation, cellular stress, inflammation, and cell regeneration.
  • These anomalies could potentially serve as therapeutic targets for the treatment and prevention of RER-STD in Standardbred racehorses.

Cite This Article

APA
Valberg SJ, Velez-Irizarry D, Williams ZJ, Henry ML, Iglewski H, Herrick K, Fenger C. (2022). Enriched Pathways of Calcium Regulation, Cellular/Oxidative Stress, Inflammation, and Cell Proliferation Characterize Gluteal Muscle of Standardbred Horses between Episodes of Recurrent Exertional Rhabdomyolysis. Genes (Basel), 13(10). https://doi.org/10.3390/genes13101853

Publication

Genes
ISSN: 2073-4425
NlmUniqueID: 101551097
Country: Switzerland
Language: English
Volume: 13
Issue: 10

Researcher Affiliations

Valberg, Stephanie J
  • Mary Anne McPhail Equine Performance Center, Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.
Velez-Irizarry, Deborah
  • Mary Anne McPhail Equine Performance Center, Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.
Williams, Zoë J
  • Mary Anne McPhail Equine Performance Center, Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.
Henry, Marisa L
  • Mary Anne McPhail Equine Performance Center, Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.
Iglewski, Hailey
  • Mary Anne McPhail Equine Performance Center, Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.
Herrick, Keely
  • Mary Anne McPhail Equine Performance Center, Department of Large Animal Clinical Sciences, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.
Fenger, Clara
  • Equine Integrated Medicine, PLC, Lexington, KY 40324, USA.

MeSH Terms

  • Animals
  • Calcium / metabolism
  • Cell Proliferation
  • Cysteine
  • Horse Diseases / genetics
  • Horses
  • Inflammation / genetics
  • Inflammation / veterinary
  • Inflammation / metabolism
  • Muscle, Skeletal / metabolism
  • Oxidative Stress
  • Purine Nucleotides / metabolism
  • Rhabdomyolysis / genetics
  • Rhabdomyolysis / veterinary
  • Rhabdomyolysis / metabolism
  • Ryanodine Receptor Calcium Release Channel

Conflict of Interest Statement

The authors declare that they have no competing interests with the contents of this article. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results”.

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Citations

This article has been cited 7 times.
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