Journal of Exercise & Organ Cross Talk
Journal of Eexercise & Organ Cross Talk

Translational research from bioinformatics to animal studies: Exploring gene expression and muscle health in COPD through selenium nanoparticles and exercise

Document Type : Original Article

Authors

Mahdi Bakhshi 1
Abdolali Bnaeifar 1
Sajjad Arshadi 1
Behzad Bazgir 2

1 Department of Physical Education and Sports Sciences, South Tehran Branch, Islamic Azad University, Tehran, Iran.

2 Exercise Physiology Research Center, Life Style Institute, Baqiyatallah University of Medical Sciences. Tehran, Iran.

https://doi.org/10.22122/jeoct.2024.485319.1129
Abstract
Recent studies highlight the role of molecular pathways, such as oxidative stress response and mitochondrial function, in COPD. This study explores the role of the PGC-1α gene, a key regulator of mitochondrial biogenesis and energy metabolism, using a rat model and bioinformatics analysis of human lung tissue samples. This study utilized a combined approach, analyzing gene expression in rat lung tissue alongside bioinformatics analysis of public human datasets. A total of 42 male Wistar rats were divided into seven groups, receiving treatments including cigarette smoke extract (CSE), nano-selenium (SeNPs), and aerobic interval training (AIT). PGC-1α expression levels were evaluated using quantitative Real-Time PCR (qRT-PCR) and analyzed using one-way ANOVA, followed by Dunnett’s post hoc test for multiple comparisons to determine significance across groups. The CSE+SeNPs+AIT group exhibited significantly higher PGC-1α expression compared to controls (p = 0.0289), indicating a potential protective role of SeNPs and exercise against oxidative stress. Bioinformatics analysis identified 250 differentially expressed genes (DEGs), with PGC-1α emerging as a critical hub gene associated with pathways like oxidative stress response and mitochondrial regulation. Protein-protein interaction (PPI) analysis further highlighted the centrality of PGC-1α in COPD pathophysiology. This study underscores the importance of PGC-1α in regulating mitochondrial function and oxidative stress in COPD. The findings suggest that PGC-1α could serve as a potential therapeutic target, offering insights into the development of interventions aimed at improving respiratory health in COPD patients. Future research should focus on validating these findings in clinical settings and exploring the therapeutic potential of PGC-1α modulation.

What is already known on this subject?

Chronic Obstructive Pulmonary Disease (COPD) is associated with  persistent inflammation, oxidative stress, and mitochondrial dysfunction, which severely impacts respiratory health.

*PGC-1α* (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha) is recognized as a critical gene involved in mitochondrial biogenesis and energy metabolism, making it a potential therapeutic target in COPD.

Previous studies have shown that selenium, a powerful antioxidant, and aerobic interval training (AIT) can independently provide protective effects against oxidative stress and improve mitochondrial health in lung tissue.

 

What this study adds?

This study identifies *PGC-1α* as a central hub gene that can be modulated by the combined effects of selenium nanoparticles (SeNPs) and AIT, which potentially synergize to counteract COPD-induced oxidative stress and mitochondrial dysfunction.

-By employing both bioinformatics and animal model analyses, the research suggests that targeting *PGC-1α* through SeNP supplementation and AIT may offer a promising therapeutic strategy for managing COPD symptoms and preserving respiratory function.

Keywords

PGC-1α
COPD
Gene expression
Oxidative stress
Bioinformatics

Subjects

Acknowledgements

We would like to express our sincere gratitude to the research staff at Sport Physiology Research Center and the laboratory team for their invaluable contributions and technical support in carrying out this study.

Funding

This study was funded by the Sport Physiology Research Center.

Compliance with ethical standards

Conflict of interest The authors declare that they have no conflict of interest.

Ethical approval This study adhered to ethical guidelines for animal research and was approved by the relevant institutional ethics committee (approval code:  IR.BMSU.REC.1400.117)

Informed consent Not applicable

Author contributions

Conceptualization: M.B, B.B, A.B; Methodology: M.B, B.B A.B; Software: M.B; Validation: M.B, A.B, B.B; Formal analysis: M.B, S.A, A.B; Investigation: M.B, B.B, A.B; Resources: M.B; Data curation: M.B, B.B; Writing - original draft: M.B, B.B, A.B; Writing - review & editing: M.B, B.B.; Visualization: M.B, S.A, A.B; Supervision: B.B, A.B, S.A; Project administration: M.B, B.B; Funding acquisition: M.B, B.B, A.B.

Agusti A., Calverley PM., Celli B, Coxson HO, Edwards LD, Lomas DA, et al. Characterisation of COPD heterogeneity in the ECLIPSE cohort. Respiratory research. 2010;11:1–14. DOI: https://doi.org/10.1186/1465-9921-11-122
Agusti A., Vogelmeier C., Faner R. COPD. (2020). changes and challenges. American Journal of Physiology-Lung Cellular and Molecular Physiology. American Physiological Society Bethesda, 319, 879-883. DOI: https://doi.org/10.1152/ajplung.00429.2020
Barbera JA, Blanco I. Chronic obstructive pulmonary disease (COPD). In: Pulmonary Circulation. CRC Press; 2016. p. 497–508.  DOI: https://doi.org/10.1201/9781315382753
Barnes P., Celli B. Systemic manifestations and comorbidities of COPD. European respiratory journal. 2009;33(5):1165–85. DOI: https://doi.org/10.1183/09031936.00128008
Castaldi PJ., Cho MH., Cohn M., Langerman F., Moran S., Tarragona N, et al. The COPD genetic association compendium: a comprehensive online database of COPD genetic associations. Human molecular genetics. 2010;19(3):526–34. DOI: https://doi.org/10.1093/hmg/ddp519
Cavailles A., Brinchault-Rabin G, Dixmier A, Goupil F, Gut-Gobert C, Marchand-Adam S, et al. Comorbidities of COPD. European Respiratory Review. 2013;22(130):454–75. DOI: https://doi.org/10.1183/09059180.00008612
Dahl M., Nordestgaard BG. Markers of early disease and prognosis in COPD. International Journal of Chronic Obstructive Pulmonary Disease. 2009;157–67. DOI: https://doi.org/10.2147/copd.s3106
Hozyen, H. F., Khalil, H. M. A., Ghandour, R. A., Al-Mokaddem, A. K., Amer, M. S., & Azouz, R. A. (2020). Nano selenium protects against deltamethrin-induced reproductive toxicity in male rats. Toxicology and Applied Pharmacology, 408, 115274. DOI: https://doi.org/10.1016/j.taap.2020.115274
Pauwels RA., Rabe KF. Burden and clinical features of chronic obstructive pulmonary disease (COPD). The Lancet. 2004;364(9434):613–20. DOI: https://doi.org/10.1016/S0140-6736(04)16855-4
Sin DD., Anthonisen N., Soriano J, Agusti A. Mortality in COPD: role of comorbidities. European Respiratory Journal. 2006;28(6):1245–57. DOI: https://doi.org/10.1183/09031936.00133805
Viegi G., Scognamiglio A., Baldacci S., Pistelli F., Carrozzi L. Epidemiology of chronic obstructive pulmonary disease (COPD). Respiration. 2001;68(1):4–19. DOI: https://doi.org/10.1159/000050456
Wan ES., Silverman EK. Genetics of COPD and emphysema. Chest. 2009;136(3):859–66. DOI: https://doi.org/10.1378/chest.09-0555
Wouters EF., Creutzberg EC., Schols AM. Systemic effects in COPD. Chest. 2002;121(5):127S-130S. DOI: https://doi.org/10.1378/chest.121.5_suppl.127s
Rehman, A., John, P., & Bhatti, A. (2021). Biogenic selenium nanoparticles: potential solution to oxidative stress mediated inflammation in rheumatoid arthritis and associated complications. Nanomaterials, 11(8), 2005. https://doi.org/10.3390/nano11082005
Pouri, S., Motamedi, H., Honary, S., & Kazeminezhad, I. (2017). Biological Synthesis of Selenium Nanoparticles and Evaluation of their Bioavailability. Braz. Arch. Biol. Technol;Braz. Arch. Biol. Technol;60: E17160452, 2017. Tab, Graf   LILACS. https://pesquisa.bvsalud.org/portal/resource/en;/biblio-951464
Sorriento, D., Di Vaia, E., & Iaccarino, G. (2021). Physical exercise: a novel tool to protect mitochondrial health. Frontiers in Physiology, 12. https://doi.org/10.3389/fphys.2021.660068
 Barchielli, G., Capperucci, A., & Tanini, D. (2022). The Role of Selenium in Pathologies: An updated review. Antioxidants, 11(2), 251. https://doi.org/10.3390/antiox11020251
Journal of Exercise & Organ Cross Talk
Volume 4, Issue 2
Spring 2024
Pages 107-116

  • Receive Date 24 March 2024
  • Revise Date 07 June 2024
  • Accept Date 12 June 2024

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