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Stem cell research & therapy2019; 10(1); 178; doi: 10.1186/s13287-019-1292-z

Nortropane alkaloids as pharmacological chaperones in the rescue of equine adipose-derived mesenchymal stromal stem cells affected by metabolic syndrome through mitochondrial potentiation, endoplasmic reticulum stress mitigation and insulin resistance alleviation.

Abstract: Equine metabolic syndrome (EMS) refers to a cluster of associated abnormalities and metabolic disorders, including insulin resistance and adiposity. The numerous biological properties of mesenchymal stem cells (MSCs), including self-renewal and multipotency, have been the subject of many in-depth studies, for the management of EMS; however, it has been shown that this cell type may be affected by the condition, impairing thus seriously their therapeutic potential. Therefore, an attempt to rescue EMS adipose-derived stem cells (ASCs) with calystegines (polyhydroxylated alkaloids) that are endowed with strong antioxidant and antidiabetic abilities was performed. ASCs isolated from EMS horses were subsequently treated with various concentrations of total calystegines. Different parameters were then assessed using flow cytometry, confocal as well as SE microscopy, and RT-qPCR. Our results clearly demonstrated that calystegines could improve EqASC viability and proliferation and significantly reduce apoptosis, via improvement of mitochondrial potentiation and functionality, regulation of pro- and anti-apoptotic pathways, and suppression of ER stress. Furthermore, nortropanes positively upregulated GLUT4 and IRS transcripts, indicating a possible sensitizing or mimetic effect to insulin. Most interesting finding in this investigation lies in the modulatory effect of autophagy, a process that allows the maintenance of cellular homeostasis; calystegines acted as pharmacological chaperones to promote cell survival. Obtained data open new perspectives in the development of new drugs, which may improve the metabolic dynamics of cells challenged by MS.
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Publication Date: 2019-06-18 PubMed ID: 31215461PubMed Central: PMC6582509DOI: 10.1186/s13287-019-1292-zGoogle Scholar: Lookup
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  • Journal Article
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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 paper investigates how a type of alkaloid, Nortropane, could potentially be utilized in the rescue of a specific type of stem cells – equine adipose-derived mesenchymal stem cells (EqASCs) – which are negatively impacted by metabolic syndrome (MS). Through laboratory study, the research found these compounds demonstrated promising effects in improving the cells’ ability to survive and reproduce, as well as their response to insulin.

Equine Adipose-derived Mesenchymal Stromal Stem Cells and Metabolic Syndrome

  • The focus of the research is on equine metabolic syndrome (EMS), a condition similar in some respects to the human metabolic syndrome, which causes increased adiposity (fatness), and insulin resistance. These conditions affect the overall well-being of horses and are a problem for horse owners and veterinarians.
  • Mesenchymal stromal stem cells (MSCs) hold promise for the treatment or management of EMS due to their ability to self-renew and differentiate into other cell types, however, their therapeutic potentials can be impaired by EMS.
  • This brings the need for a method to “rescue” these cells i.e., to restore their therapeutic potentials.

The Role of Nortropane Alkaloids

  • Enter nortropane alkaloids, specifically, calystegines—a type of compound that has strong antioxidant and anti-diabetic abilities. The researchers used different concentrations of calystegines to treat the impaired stem cells from horses with EMS.
  • The treated cells were then analyzed using flow cytometry, microscopy techniques, and molecular biology methods to assess various parameters.
  • The results show a significant improvement in EqASC viability and proliferation, and a reduction in apoptosis (cell death).

The Mechanisms Involved

  • The mechanisms through which this rescue was achieved fans out to cover many aspects of cell health:
  • Improvement of mitochondrial potentiation and functionality – mitochondria is the power house of the cell and any improvement to its function can boost cell health.
  • Regulation of cell death pathways – the calystegines appeared to rebalance the process of apoptosis and cell survival.
  • Suppression of endoplasmic reticulum (ER) stress – ER is an essential part of the cell responsible for protein synthesis and maturation. Stress or dysfunction in this part of the cell can lead to disease.
  • In addition, nortropanes appeared to have a positive effect on the regulation of GLUT4 and IRS transcripts, providing potential sensitizing or mimetic effects to insulin.

Potential Impact of the Research

  • Of note, the researchers found that calystegines have a modulatory effect on autophagy—an important process by which cells maintain homeostasis by removing damaged or unneeded cellular components. They acted as pharmacological chaperones to promote cell survival.
  • This study could open new perspectives in the development of drugs to improve the metabolic dynamics of cells challenged by MS and potentially broaden the applications of MSCs in regenerative medicine.

Cite This Article

APA
Bourebaba L, Bedjou F, Röcken M, Marycz K. (2019). Nortropane alkaloids as pharmacological chaperones in the rescue of equine adipose-derived mesenchymal stromal stem cells affected by metabolic syndrome through mitochondrial potentiation, endoplasmic reticulum stress mitigation and insulin resistance alleviation. Stem Cell Res Ther, 10(1), 178. https://doi.org/10.1186/s13287-019-1292-z

Publication

Stem cell research & therapy
ISSN: 1757-6512
NlmUniqueID: 101527581
Country: England
Language: English
Volume: 10
Issue: 1
Pages: 178
PII: 178

Researcher Affiliations

Bourebaba, Lynda
  • Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Norwida 27B, 50-375, Wrocław, Poland. lynda.bourebaba@upwr.edu.pl.
  • International Institute of Translational Medicine, Jesionowa, 11, Malin, 55-114, Wisznia Mała, Poland. lynda.bourebaba@upwr.edu.pl.
Bedjou, Fatiha
  • Laboratoire de Biotechnologies végétales et d'Ethnobotanique, Faculté des Sciences de la Nature et de la Vie, Université de Bejaia, 06000, Bejaia, Algeria.
Röcken, Michael
  • Faculty of Veterinary Medicine, Equine Clinic - Equine Surgery, Justus-Liebig-University, 35392, Gießen, Germany.
Marycz, Krzysztof
  • Department of Experimental Biology, Faculty of Biology and Animal Science, Wrocław University of Environmental and Life Sciences, Norwida 27B, 50-375, Wrocław, Poland. krzysztof.marycz@upwr.edu.pl.
  • Faculty of Veterinary Medicine, Equine Clinic - Equine Surgery, Justus-Liebig-University, 35392, Gießen, Germany. krzysztof.marycz@upwr.edu.pl.
  • International Institute of Translational Medicine, Jesionowa, 11, Malin, 55-114, Wisznia Mała, Poland. krzysztof.marycz@upwr.edu.pl.

MeSH Terms

  • Adipose Tissue / cytology
  • Alkaloids / pharmacology
  • Animals
  • Apoptosis / drug effects
  • Cell Proliferation / drug effects
  • Endoplasmic Reticulum Stress / drug effects
  • Flow Cytometry
  • Gas Chromatography-Mass Spectrometry
  • Horses
  • Insulin Resistance
  • Membrane Potential, Mitochondrial / drug effects
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Metabolic Syndrome / metabolism
  • Nortropanes / pharmacology
  • Reactive Nitrogen Species / metabolism
  • Reactive Oxygen Species / metabolism
  • Tropanes / pharmacology

Conflict of Interest Statement

The authors declare that they have no competing interests.

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Citations

This article has been cited 8 times.
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